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At least 1,153 records · Page 64Linked to original sources
PubMed1998

Dopamine D1B receptor chimeras reveal modulation of partial agonist activity by carboxyl-terminal tail sequences.

NNC 01-0012, a second-generation benzazepine compound, pharmacologically differentiates multiple vertebrate D1 receptor subtypes (D1A, D1B, D1C, and D1D) and displays high selectivity and affinity for dopamine D1C receptors. Functionally, whereas NNC 01-0012 acts as a full or poor antagonist at D1C and D1A receptor-mediated cyclic AMP production, respectively, it exhibits partial agonist activity at the D1B receptor. To define some of the structural motifs that regulate the pharmacological and functional differentiation of vertebrate dopamine D1 receptors by NNC 01-0012, a series of receptor chimeras were constructed in which the divergent carboxyl-terminal (CT) receptor tails were replaced with the corresponding sequences of D1A, D1B, or D1C receptors. Substitution of the vertebrate D1B carboxyl-terminal-tail at position Tyr345 with carboxyl-terminal-tail sequences of the D1A receptor abolished the partial agonist activity of NNC 01-0012 without affecting dopamine-stimulated cyclic AMP accumulation. At vertebrate D1B/D1CcT-tail receptor mutants, however, the intrinsic activity of the partial agonist NNC 01-0012 (10 microM) was markedly enhanced (approximately 60% relative to 10 microM dopamine) with no concomitant alteration in the molecule's ligand binding affinity or constitutive activity of the chimeric receptor. Similar results were obtained with other benzazepines such as SKF-38393 and SCH-23390, which act as partial agonists at vertebrate D1B receptors. Substitution of D1A and D1C receptor carboxyl-terminal tails with sequences encoded by the D1B receptor carboxyl-terminal tail did not, however, produce receptors with functional characteristics significantly different from wild type. Taken together, these data clearly suggest that in addition to well-characterized domains and amino acid residues in the third cytoplasmic loop, partial agonist activity at the D1B receptor is modulated by sequence-specific motifs within the carboxyl-terminal tail, a region that may underlie the possible structural basis for functionally divergent roles of multiple dopamine D1-like receptors.

Animals↗
PubMed2003

Rapid divergence of the ecdysone receptor in Diptera and Lepidoptera suggests coevolution between ECR and USP-RXR.

Ecdysteroid hormones are major regulators in reproduction and development of insects, including larval molts and metamorphosis. The functional ecdysone receptor is a heterodimer of ECR (NR1H1) and USP-RXR (NR2B4), which is the orthologue of vertebrate retinoid X receptors (RXR alpha, beta, gamma). Both proteins belong to the superfamily of nuclear hormone receptors, ligand-dependent transcription factors that share two conserved domains: the DNA-binding domain (DBD) and the ligand-binding domain (LBD). In order to gain further insight into the evolution of metamorphosis and gene regulation by ecdysone in arthropods, we performed a phylogenetic analysis of both partners of the heterodimer ECR/USP-RXR. Overall, 38 USP-RXR and 19 ECR protein sequences, from 33 species, have been used for this analysis. Interestingly, sequence alignments and structural comparisons reveal high divergence rates, for both ECR and USP-RXR, specifically among Diptera and Lepidoptera. The most impressive differences affect the ligand-binding domain of USP-RXR. In addition, ECR sequences show variability in other domains, namely the DNA-binding and the carboxy-terminal F domains. Our data provide the first evidence that ECR and USP-RXR may have coevolved during holometabolous insect diversification, leading to a functional divergence of the ecdysone receptor. These results have general implications on fundamental aspects of insect development, evolution of nuclear receptors, and the design of specific insecticides.

Amino Acid Sequence↗
PubMed1998

Glycyl-tRNA synthetase from Thermus thermophilus--wide structural divergence with other prokaryotic glycyl-tRNA synthetases and functional inter-relation with prokaryotic and eukaryotic glycylation systems.

The tRNA glycylation system is amongst the most complex aminoacylation systems since neither the oligomeric structure of the enzymes nor the discriminator base in tRNAs are conserved in the phylae. To understand better this structural diversity and its functional consequences, the prokaryotic glycylation system from Thermus thermophilus, an extreme thermophile, was investigated and its structural and functional inter-relations with those of other origins analyzed. Alignments of the protein sequence of the dimeric thermophilic glycyl-tRNA synthetase (Gly-tRNA synthetase) derived from its gene with sequences of other dimeric Gly-tRNA synthetases revealed an atypical character of motif 1 in all these class 2 synthetases. Interestingly, the sequence of the prokaryotic thermophilic enzyme resembles eukaryotic and archaebacterial Gly-tRNA synthetases, which are all dimeric, and diverges drastically from the tetrameric enzymes from other prokaryotes. Cross aminoacylations with tRNAs and synthetases of different origins provided information about functional interrelations between the glycylation systems. Efficient glycylations involving partners from T. thermophilus and Escherichia coli showed conservation of the recognition process in prokaryotes despite strong structural variations of the synthetases. However, Gly-tRNA synthetase from T. thermophilus acylates eukaryotic tRNA(Gly) while the charging ability of the E. coli enzyme is restricted to prokaryotic tRNA(Gly). A similar behaviour is found in eukaryotic systems where the restricted species specificity for tRNA glycylation of mammalian Gly-tRNA synthetase contrasts with the relaxed specificity of the yeast enzyme. The consensus sequence of the tRNAs charged by the various Gly-tRNA synthetases reveals conservation of only G1-C72 in the acceptor arm, C35 and C36 in the anticodon, and the (G10-Y25)-G45 triplet involved in tRNA folding. Conservation of these nucleotides indicates their key role in glycylation and suggests that they were part of the ancestral glycine identity set. These features are discussed in the context of the phylogenic connections between prokaryotes, eukaryotes, and archaebacteria, and of the particular place of T. thermophilus in this phylogeny.

Amino Acid Sequence↗
PubMedDate not supplied

Genetic divergence between mouse and humans: a useful direction for gene pathway analysis.

Preliminary results in comparative genetics have revealed a growing list of differences between mice and humans (Strachan et al. [1997]: Nat. Genet. 16:126-132). However, it is increasingly apparent that some of these differences are not accompanied by changes in function. Such differences are nevertheless useful because they represent a sort of genetic experiment that provides evidence helpful in deducing how the genetic circuits work. This article draws attention to some recent results. First, we briefly report on representative examples of genetic differences between rodents and humans, suggesting, as expected, that such divergence is abundant and diverse at all levels of gene regulation. Second, on the basis of a more detailed analysis bearing on four examples, we emphasize that the study of genetic differences associated with little or no functional divergence is likely to be a profitable direction for future analysis of genetic pathways. Finally, we suggest that apparently nonfunctional genetic divergence may underlie different susceptibilities to disease. A detailed knowledge of human-mouse genetic divergence will provide an indispensable framework for extrapolating the molecular effects of mutations and teratogens from mice to humans in studies of abnormal development.

Animals↗
PubMed1997

Divergence and conservation of the partitioning and global regulation functions in the central control region of the IncP plasmids RK2 and R751.

The central control region (Ctl) of IncP plasmids is associated with two phenotypes: the coordinate expression of replication and transfer genes; and the ability to increase the segregational stability of a low-copy number test plasmid. This region of the IncP beta plasmid R751 shows significant sequence divergence from the IncP alpha plasmid RK2 sequence, and two genes, korF and korG, present in the IncP alpha region are missing in the IncP beta Ctl. In other respects the organization of the Ctl is basically the same. Although the two key global regulatory genes korA and korB are highly conserved, studies on their ability to repress transcription from a variety of IncP alpha and IncP beta plasmid promoters suggest differences in operator recognition by KorA and synergy with other repressors. The products of kfrA, upf54.8 and upf54.4 genes are conserved; KfrA shows least conservation and, while retaining the ability to act as a transcriptional repressor, appears to have completely different DNA-binding specificity. The genes required for the plasmid segregational stabilization (partitioning) phenotype--incC, korB and the korB operator OB3--are conserved and contribute to a more efficient plasmid stabilization than the IncP alpha equivalents. This may indicate that the Ctl plays an especially important role in partitioning of IncP beta plasmids, since they lack the second stability region (parlmrs) found in IncP alpha plasmids.

Bacterial Proteins↗
PubMed2006

Xenopus Zic4: conservation and diversification of expression profiles and protein function among the Xenopus Zic family.

We compared the expression and function of Xenopus Zic4 with those of the other four Xenopus laevis Zic family members (Zic1, Zic2, Zic3, and Zic5). Zic4 expression was detected mainly in the neural plate border, dorsal neural tube, and somites, and was similar to that of Zic1, which is adjacent to Zic4 on the same chromosome. Injection of wild-type or mutant Zic4 RNA caused the induction of neural crest marker gene expression, hyperplastic neural tissue, and ectopic pigment cell formation, indicating that Zic4 can induce neural and neural crest tissue, as can other Xenopus Zic genes. Deletion analysis showed that the zinc-finger domain is critical for many Zic4 functions, but the C-terminal region is differently involved in induction of two neural crest markers, Slug and Sox10. The protein function as determined by the animal cap explant assay was similar to that of Zic5, but different from those of Zic1, Zic2, and Zic3, suggesting that Xenopus Zic genes can be divided into two groups based on function. These results indicate that the five Xenopus Zic genes cooperatively regulate both neural and neural crest development, despite significantly diverged expression profiles and functions.

Amino Acid Sequence↗
PubMed2004

Hazard identification and predictability of children's health risk from animal data.

Children differ from adults both physiologically and behaviorally. These differences can affect how and when exposures to xenobiotics occur and the resulting responses. Testing using animal models may be used to predict whether children display novel toxicities not observed in adults or whether children are more or less sensitive to known toxicities. Historically, evaluation of developmental toxicity has focused on gestational exposures and morphological changes resulting from this exposure. Functional consequences of gestational exposure and postnatal exposure have not been as well studied. Difficulties with postnatal toxicity evaluations include divergent differentiation of structure, function and physiology across species, lack of understanding of species differences in functional ontogeny, and lack of common end points and milestones across species.

Animals↗
PubMed2002

Comparative endocrinology of the insulin-like growth factor-binding protein.

Emerging early in chordate evolution, the IGF-regulatory axis diverged from an insulin-like predecessor into a vertebrate regulatory system specializing in cell growth activation and allied anabolic functions. Essential to the divergence of the IGF and insulin systems was an early presence of soluble IGF-binding proteins (IGFBPs), which bind IGF peptides at much higher affinity than that of the insulin receptor but at comparable affinities to that of the IGF receptor. IGFBPs have no homology with IGF receptors. Instead, IGFBPs are a derived group of proteins within a superfamily of cysteine-rich growth factors, whose members are found throughout the animal taxa. While blocking IGF actions through the insulin receptor is a fundamental role, IGFBPs evolved within the vertebrate line into centralized, 'integrators' of the endocrine growth-regulatory apparatus. IGFBPs have substantial influences on the distribution and bioavailability of IGF peptides in the cellular and physiological environments, but they have a variety of other properties. The six principal mammalian IGFBPs exhibit an array of specialized properties that appear to be derived from a complex evolutionary history (including cell membrane association, interaction with proteins that post-translationally modify them, direct IGF-independent effects on cells, and others) and they are regulated by a diversity of 'outside' factors (e.g. other hormones, metabolic status, stress). Thus, IGFBPs are multifunctional integrators having diverse physiological 'agendas'. Much less is known about IGFBPs and their properties in the other vertebrate taxa. Increasingly, however, it is being recognized that they play equally important endocrine roles, in both conserved and non-conserved ways, when compared with those currently defined in mammals. This review highlights selected 'comparative aspects' in current IGFBP research, in an attempt to view this essential group of endocrine regulators from a wider, biological perspective.

Animals↗
PubMedDate not supplied

[Hypothesis of possible evolution and functional specialization based on the recombination and transposition of elementary functional blocks].

A number of examples demonstrating that different cell and organ functions are being performed by a limited set of identical or similar functional blocks has been analysed. The latters are molecular or supramolecular structures fulfilling elementary functions. Functional evolution, functional and structural specializations, divergence, convergence and other processes have been considered as associated largely with the relationship, recombination and transposition of such elementary functional blocks, presumably, originated at the early stages of evolution.

Animals↗
PubMed1995

The marine red alga Chondrus crispus has a highly divergent beta-tubulin gene with a characteristic 5' intron: functional and evolutionary implications.

We characterized a nuclear gene and its corresponding cDNA encoding beta-tubulin (gene TubB1) of the marine red alga Chondrus crispus. The deduced TubB1 protein is the most divergent beta-tubulin so far reported with only 64 to 69% amino acid identity relative to other beta-tubulins from higher and lower eukaryotes. Our analysis reveals that TubB1 has an accelerated evolutionary rate probably due to a release of functional constraints in connexion with a specialization of microtubular structures in rhodophytes. It further indicates that isoform diversity and functional differentiation of tubulins in eukaryotic cells may be controlled by independent selective constraints. TubB1 has a short spliceosomal intron at its 5' end which seems to be a characteristic feature of nuclear protein-coding genes from rhodophytes. The splice junctions of the four known rhodophyte introns comply well with the corresponding consensus sequences of higher plants in agreement with previous suggestions from phylogenetic inference that red algae and green plants may be sister groups. The paucity and asymmetrical location of introns in rhodophyte genes can be explained by differential intron loss due to conversion of genes by homologous recombination with cDNAs corresponding to reverse transcribed mRNAs or partially spliced pre-mRNAs, respectively. The identification of an intron containing TubB1 cDNA in C. crispus confirms that pre-mRNAs can escape both splicing and degradation in the nucleus prior to transport into the cytoplasm. Differential Southern hybridizations under non-stringent conditions with homologous and heterologous probes suggest that C. crispus contains a second degenerate beta-tubulin gene (or pseudogene?) which, however, is only distantly related to TubB1 as it is to the more conserved homologues of other organisms.

Amino Acid Sequence↗
PubMed1999

Mutation, recombination, and incipient speciation of bacteria in the laboratory.

Mutations in the DNA mismatch repair system increase mutation and recombination. They may thereby promote the genetic divergence that underlies speciation, after which the reacquisition of a functional repair system may sustain that divergence by creating a barrier to recombination. We tested several lines of Escherichia coli, derived from a common ancestor and evolved for 20,000 generations, for their recombination ability. Some lines, but not others, had become mismatch repair-defective mutators during experimental evolution, providing different opportunities for DNA sequence divergence. We knocked out the repair system in lines that had retained this function, and we restored function to those lines that had become defective. We then estimated recombination rates in various crosses between these repair-deficient and -proficient strains. The effect of the mismatch repair system on recombination was greatest in those lines that had evolved nonfunctional repair, indicating they had undergone more sequence divergence and, consequently, were more sensitive to the recombination-inhibiting effect of a functional repair system. These results demonstrate the establishment of an incipient genetic barrier between formerly identical lines, and they support a model in which the mismatch repair system can influence speciation dynamics through its simultaneous effects on mutation and recombination.

Biological Evolution↗
PubMed1995

Structural repertoire in VH pseudogenes of immunoglobulins: comparison with human germline genes and human amino acid sequences.

In the pool of human immunoglobulin VH gene segments, pseudogenes amount to roughly 30% of the total number of genes. Some of them are highly conserved among unrelated individuals. These facts suggest a possible functional role for pseudogenes in the human immune response diversity. This paper intends to provide additional information about the structure of VH pseudogene sequences to evaluate the possible role of pseudogenes in the immune response. Mutations capable of altering framework stability in human VH pseudogenes were analyzed. Results indicate that VH pseudogenes are about 14 times as divergent as human VH functional germline genes on the one hand, and four times as divergent in the case of human VH amino acid sequences on the other. The high number of disruptive mutations in pseudogenes is an expected result because of the lack of functionality of these genes. In the second part of the work we analyze whether or not the same takes place in the positions that determine the existence of canonical structures in the hypervariable loops in VH pseudogenes. An extension of such analysis is applied to all species with reported VH pseudogenes. In contrast with results concerning framework positions, 69% of known human VH pseudogenes have canonical structures in the first hypervariable loop, while 48% do so in the second one. Comparison of these results with those found in human VH functional germline genes and human VH amino acid sequences shows that in the former as many as 100% and in the latter 96% have canonical structures. In VH amino acid sequences the result is similar to pseudogenes for H1. For H2, such value lies between the percentage of germline genes (96%) and the percentage of pseudogenes (48%). The possible significance of the existence of canonical structures in the hypervariable loops of VH pseudogenes is discussed.

Amino Acid Sequence↗
PubMed1989

Dual bidirectional promoters at the mouse dhfr locus: cloning and characterization of two mRNA classes of the divergently transcribed Rep-1 gene.

The mouse dihydrofolate reductase gene (dhfr) is a housekeeping gene expressed under the control of a promoter region embedded in a CpG island--a region rich in unmethylated CpG dinucleotides. A divergent transcription unit exists immediately upstream of the dhfr gene which is coamplified with dhfr in some but not all methotrexate-resistant cell lines. We show that the promoter region for this gene pair consists of two bidirectional promoters, a major and minor promoter, which are situated within a 660-base-pair region upstream of the dhfr ATG translation initiation codon. The major promoter controls over 90% of dhfr transcription, while the minor promoter directs the transcription of the remaining dhfr mRNAs. The major promoter functions bidirectionally, transcribing a divergent 4.0-kilobase poly(A) mRNA (class A) in the direction opposite that of dhfr transcription. The predicted protein product of this mRNA is 105 kilodaltons. The minor promoter also functions bidirectionally, directing the transcription of at least two divergent RNAs (class B). These RNAs, present in quantities approximately 1/10 to 1/50 that of the class A mRNAs, are 4.4- and 1.6-kilobase poly(A) mRNAs. cDNAs representing both class A and class B mRNAs have been cloned from a mouse fibroblast cell line which has amplified the dhfr locus (3T3R500). DNA sequence analysis of these cDNAs reveals that the class A and class B mRNAs share, for the most part, the same exons. On the basis of S1 nuclease protection analysis of RNA preparations from several mouse tissues, both dhfr and divergent genes showed similar levels of expression but did show some specificity in start site utilization. Computer homology searches have revealed sequence similarity of the divergent transcripts with bacterial genes involved in DNA mismatch repair, and we therefore have named the divergently transcribed gene Rep-1.

Amino Acid Sequence↗
PubMed2000

Nonrandom spatial distribution of synonymous substitutions in the GP63 gene from Leishmania.

In this work we analyze the variability in substitution rates in the GP63 gene from Leishmania. By using a sliding window to estimate substitution rates along the gene, we found that the rate of synonymous substitutions along the GP63 gene is highly correlated with both the rate of amino acid substitution and codon bias. Furthermore, we show that comparisons involving genes that represent independent phylogenetic lines yield very similar divergence/conservation patterns, thus suggesting that deterministic forces (i.e., nonstochastic forces such as selection) generated these patterns. We present evidence indicating that the variability in substitution rates is unambiguously related to functionally relevant features. In particular, there is a clear relationship between rates and the tertiary structure of the encoded protein since all divergent segments are located on the surface of the molecule and facing one side (almost parallel to the cell membrane) on the exposed surface of the organism. Remarkably, the protein segments encoded by these variable regions encircle the active site in a funnel-like distribution. These results strongly suggest that the pattern of nucleotide divergence and, notably, of synonymous divergence is affected by functional constraints.

Animals↗
PubMed1999

Highly divergent amino termini of the homologous human ALR and yeast scERV1 gene products define species specific differences in cellular localization.

The yeast scERV1 gene product is involved in the biogenesis of mitochondria and is indispensable for viability and regulation of the cell cycle. Recently the general importance of this gene for the eukaryotic cell was shown by the identification of a structural and functional human homologue. The homologous mammalian ALR (Augmenter of Liver Regeneration) genes from man, mouse and rat are involved in the phenomenon of liver regeneration. A low expression rate of the genes is found in all investigated cells and mammalian tissues but it is specifically induced after damage of liver organs and is especially high during spermatogenesis. The alignment of the different proteins identifies a highly conserved carboxy terminus with more than 40% identical amino acids between yeast and mammals. The conserved carboxy terminus is functionally interchangeable between distantly related species like yeast and man. In contrast, the amino terminal parts of the proteins display a high degree of variability and significant differences even among closely related species. This finding leads to the problem whether the amino termini have comparable or divergent functions in different species. In this study we demonstrate by heterologous complementation experiments in yeast that the complete human ALR protein with its own amino terminus is not able to substitute for the yeast scERV1 protein. Fusion proteins of Alrp and scErv1p with the green fluorescence protein were created to investigate the respective subcellular localizations of these homologous proteins in yeast and human cells. In yeast cells human Alrp accumulates in the cytoplasm in contrast to yeast scErv1p that is preferentially associated with yeast mitochondria. Comparable studies with human cells clearly show that the homologous human Alrp is located in the cytosol of these cells. Fractionation experiments and antibody tests with yeast and human mitochondria and cellular extracts verify these findings.

Amino Acid Sequence↗
PubMed2006

Identification of an N-terminal transactivation domain of Runx1 that separates molecular function from global differentiation function.

RUNX1, or AML1, is a transcription factor that is the most frequent target for chromosomal gene translocations in acute leukemias. RUNX1 is essential for definitive hematopoiesis in embryos and profoundly influences adult steady-state hematopoiesis both positively and negatively. To investigate this wide range of normal activities and the pathological role of RUNX1, it is important to define the functions of different domains of the protein. RUNX1, RUNX2, and RUNX3 are highly conserved in their DNA binding runt homology domain and contain divergent sequences of unknown function N-terminal to this domain. Here we analyzed the role of the N-terminal sequence and the alpha-helix of the runt homology domain of Runx1 in DNA binding, transactivation, and megakaryocytopoiesis. Both the N terminus and the alpha-helix were found to reduce DNA binding of Runx1 and be essential for transactivation of the granulocyte-macrophage colony-stimulating factor and Ialpha1 promoters by Runx1. The N terminus of Runx1, including the alpha-helix, was also required for transactivation of a Gal4 reporter when expressed as fusion proteins with a Gal4 DNA binding domain, and the N terminus alone was capable of stimulating transcription when fused to the Gal4 DNA binding domain. The N terminus and the alpha-helix, however, were not required for megakaryocyte development from embryonic stem cells differentiated in vitro. Thus, our findings define a second transactivation domain of Runx1 that is differentially required for activation of transcription of some Runx1-dependent promoters and megakaryocytopoiesis.

Cell Differentiation↗
PubMed2006

Isolation and expression patterns of LATERAL ORGAN BOUNDARIES-like genes in Lotus japonicus.

A shoot apical meristem (SAM) is composed of several distinct domains and lateral organs are initiated at the peripheral zone during plant development. Establishment and maintenance of boundary between SAM and lateral organs is an important developmental process, in which many regulators are involved. LATERAL ORGAN BOUNDARIES (LOB) in Arabidopsis, displaying a specific expression pattern corresponding to the boundary of developmental lateral organs, belongs to a large gene family--LOB domain gene family, which encode proteins with a conserved LOB domain at the N-terminus. Beside LOB, other members of this gene family are also involved in divergent developmental processes in Arabidopsis. To investigate the functions of LOB-like genes in the distantly related legumes, we isolated LjLOBs from a model legume plant Lotus japonicus, and conducted RNA in situ hybridization to investigate their expression patterns. It was found that LjLOB1 and LjLOB3 were strongly expressed at the bases of leaflet primordia, which coincided with the boundaries between leaflet primordia and compound leaf meristem, while LjLOB4 was expressed at the boundaries between whorls in the developing floral bud. The different special expression patterns of LjLOBs strongly suggest that their functions in L. japonicus may be divergent: LjLOB1 and LjLOB3 could play important roles in the control of compound leaf development, and LjLOB4 may be required during floral development.

Amino Acid Sequence↗
PubMed2005

Comparison of class A and D G protein-coupled receptors: common features in structure and activation.

All G protein-coupled receptors (GPCRs) share a common seven TM helix architecture and the ability to activate heterotrimeric G proteins. Nevertheless, these receptors have widely divergent sequences with no significant homology. We present a detailed structure-function comparison of the very divergent Class A and D receptors to address whether there is a common activation mechanism across the GPCR superfamily. The Class A and D receptors are represented by the vertebrate visual pigment rhodopsin and the yeast alpha-factor pheromone receptor Ste2, respectively. Conserved amino acids within each specific receptor class and amino acids where mutation alters receptor function were located in the structures of rhodopsin and Ste2 to assess whether there are functionally equivalent positions or regions within these receptors. We find several general similarities that are quite striking. First, strongly polar amino acids mediate helix interactions. Their mutation generally leads to loss of function or constitutive activity. Second, small and weakly polar amino acids facilitate tight helix packing. Third, proline is essential at similar positions in transmembrane helices 6 and 7 of both receptors. Mapping the specific location of the conserved amino acids and sites of constitutively active mutations identified conserved microdomains on transmembrane helices H3, H6, and H7, suggesting that there are underlying similarities in the mechanism of the widely divergent Class A and Class D receptors.

Amino Acid Sequence↗