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PubMed2002

Sequence conservation in Ig-like domains: the role of highly conserved proline residues in the fibronectin type III superfamily.

The role of conserved proline residues in fibronectin type III (fnIII) domains is investigated. Surprisingly, none of the standard set of explanations for residue conservation applies. The proline residues are not apparently conserved for function, or stability, or to nucleate folding, or to promote stabilising interactions across domain boundaries. However, when the most highly conserved proline residues are mutated to alanine there is an increase in the rate of aggregation of a fnIII double-module construct. The results suggest that proline residues may be conserved at domain-domain boundaries in fnIII domains to prevent aggregation in multi-modular proteins.

Amino Acid Motifs↗

PubMed2006

Conservation of intrinsic disorder in protein domains and families: I. A database of conserved predicted disordered regions.

Many protein regions have been shown to be intrinsically disordered, lacking unique structure under physiological conditions. These intrinsically disordered regions are not only very common in proteomes, but also crucial to the function of many proteins, especially those involved in signaling, recognition, and regulation. The goal of this work was to identify the prevalence, characteristics, and functions of conserved disordered regions within protein domains and families. A database was created to store the amino acid sequences of nearly one million proteins and their domain matches from the InterPro database, a resource integrating eight different protein family and domain databases. Disorder prediction was performed on these protein sequences. Regions of sequence corresponding to domains were aligned using a multiple sequence alignment tool. From this initial information, regions of conserved predicted disorder were found within the domains. The methodology for this search consisted of finding regions of consecutive positions in the multiple sequence alignments in which a 90% or more of the sequences were predicted to be disordered. This procedure was constrained to find such regions of conserved disorder prediction that were at least 20 amino acids in length. The results of this work included 3,653 regions of conserved disorder prediction, found within 2,898 distinct InterPro entries. Most regions of conserved predicted disorder detected were short, with less than 10% of those found exceeding 30 residues in length.

Amino Acid Sequence↗

PubMed1977

Semi-conservative and non-conservative replication of DNA in temperature-sensitive mouse L-cells.

The mode of DNA replication has been studied in wild-type mouse L-cells (WT-4) and in two subclones (TS A1S9 and ts C1 cells) which are temperature-sensitive in DNA synthesis. It has been demonstrated that DNA is replicated by the semi-conservative mechanism in WT-4 cells grown at 34 degrees C or at 38.5 degrees C throughout the logarithmic phase and into the stationary phase. Similar results were obtained with ts A1S9 and ts C1 cells grown at the permissive temperature (34 degrees C). When the latter cells were incubated at the non-permissive temperature (38.5 degrees C) inactivation of DNA synthesis appeared to proceed through three general stages. During the first 24 h after temperature upshift suppression of semi-conservative DNA replication occurred. During the second stage a very low level of semi-conservative synthesis was maintained. During the third stage, incorporation of dThd into DNA began to increase, often reaching 10-20% of control levels after 3-5 days. During this third stage DNA synthesis was effected by a non-conservative mechanism. Temperature-inactivated ts A1S9 cells and ts C1 cells were able to perform semi-conservative synthesis upon back-shift to 34 degrees C, using as template that DNA synthesized prior to temperature upshift.

Centrifugation, Density Gradient↗

PubMed2003

The PUF family of RNA-binding proteins: does evolutionarily conserved structure equal conserved function?

Drosophila Pumilio (Pum) protein is a founder member of a novel family of RNA-binding proteins, known as the PUF family. The PUF proteins constitute an evolutionarily highly conserved family of proteins present from yeast to humans and plants, and are characterized by a highly conserved C-terminal RNA-binding domain, composed of eight tandem repeats. The conserved biochemical features and genetic function of PUF family members have emerged from studies of model organisms. PUF proteins bind to related sequence motifs in the 3' untranslated region (3'UTR) of specific target mRNAs and repress their translation. Frequently, PUF proteins function asymmetrically to create protein gradients, thus causing asymmetric cell division and regulating cell fate specification. Thus, it was recently proposed that the primordial role of PUF proteins is to sustain mitotic proliferation of stem cells. Here we review the evolution, conserved genetic and biochemical properties of PUF family of proteins, and discuss protein interactions, upstream regulators and downstream targets of PUF proteins. We also suggest that a conserved mechanism of PUF function extends to the newly described mammalian members of the PUF family (human PUM1 and PUM2, and mouse Pum1 and Pum2), that show extensive homology to Drosophila Pum, and could have an important role in cell development, fate specification and differentiation.

3' Untranslated Regions↗

PubMed2025

Conservation genomics of a threatened subtropical Rhododendron species highlights the distinct conservation actions required in marginal and admixed populations.

With the impact of climate change and anthropogenic activities, the underlying threats facing populations with different evolutionary histories and distributions, and the associated conservation strategies necessary to ensure their survival, may vary within a species. This is particularly true for marginal populations and/or those showing admixture. Here, we re-sequence genomes of 102 individuals from 21 locations for Rhododendron vialii, a threatened species distributed in the subtropical forests of southwestern China that has suffered from habitat fragmentation due to deforestation. Population structure results revealed that R. vialii can be divided into five genetic lineages using neutral single-nucleotide polymorphisms (SNPs), whereas selected SNPs divide the species into six lineages. This is due to the Guigu (GG) population, which is identified as admixed using neutral SNPs, but is assigned to a distinct genetic cluster using non-neutral loci. R. vialii has experienced multiple genetic bottlenecks, and different demographic histories have been suggested among populations. Ecological niche modeling combined with genomic offset analysis suggests that the marginal population (Northeast, NE) harboring the highest genetic diversity is likely to have the highest risk of maladaptation in the future. The marginal population therefore needs urgent ex situ conservation in areas where the influence of future climate change is predicted to be well buffered. Alternatively, the GG population may have the potential for local adaptation, and will need in situ conservation. The Puer population, which carries the heaviest genetic load, needs genetic rescue. Our findings highlight how population genomics, genomic offset analysis, and ecological niche modeling can be integrated to inform targeted conservation.

Rhododendron↗

PubMed1997

Structure-function relationships within the peptide deformylase family. Evidence for a conserved architecture of the active site involving three conserved motifs and a metal ion.

Thermus thermophilus peptide deformylase was characterized. Its enzymatic properties as well as its organization in domains proved to share close resemblances with those of the Escherichia coli enzyme despite few sequence identities. In addition to the HEXXH signature sequence of the zinc metalloprotease family, a second short stretch of strictly conserved amino acids was noticed, EGCLS, the cysteine of which corresponds to the third zinc ligand. The study of site-directed mutants of the E. coli deformylase shows that the residues of this stretch are crucial for the structure and/or catalytic efficiency of the active enzyme. Both aforementioned sequences were used as markers of the peptide deformylase family in protein sequence databases. Seven sequences coming from Haemophilus influenzae, Lactococcus lactis, Bacillus stearothermophilus, Mycoplasma genitalium, Mycoplasma pneumoniae, Bacillus subtilus and Synechocystis sp. could be identified. The characterization of the product of the open reading frame from B. stearothermophilus confirmed that it actually corresponded to a peptide deformylase with properties similar to those of the E. coli enzyme. Alignment of the nine peptide deformylase sequences showed that, in addition to the two above sequences, only a third one, GXGXAAXQ, is strictly conserved. This motif is also located in the active site according to the three-dimensional structure of the E. coli enzyme. Site-directed variants of E. coli peptide deformylase showed the involvement of the corresponding residues for maintaining an active and stable enzyme. Altogether, these data allow us to propose that the three identified conserved motifs of peptide deformylases build up the active site around a metal ion. Finally, an analysis of the location of the other conserved residues, in particular of the hydrophobic ones, was performed using the three-dimensional model of the E. coli enzyme. This enables us to suggest that all bacterial peptide deformylases adopt a constant overall tertiary structure.

Amidohydrolases↗

PubMed1995

Self peptides bound by HLA class I molecules are derived from highly conserved regions of a set of evolutionarily conserved proteins.

An evolutionary analysis of self peptides reported to be bound by HLA class I molecules showed that these peptides are largely derived from proteins that have been highly conserved in the history of mammals. These proteins also often have universal tissue expression and have a higher than average frequency of highly hydrophilic residues. The peptides themselves are generally still more highly conserved than the source proteins and have a higher frequency of highly hydrophobic residues, evidently often being derived from conserved hydrophobic cores of the source proteins. These results suggest that the mechanism by which peptides are derived for MHC presentation may preferentially select peptides from conserved protein regions. In the case of parasite-derived peptides, such a mechanism would be adaptive in that it would reduce the likelihood of escape mutants.

Animals↗

PubMed2005

Highly conserved regulatory elements around the SHH gene may contribute to the maintenance of conserved synteny across human chromosome 7q36.3.

Comparative genomic analysis reveals an exceptionally large section of conserved shared synteny between the human 7q36 chromosomal region and the pufferfish (Fugu rubripes) genome. Remarkably, this conservation extends not only to gene order across 16 genes, but also to the position and orientation of a number of prominent conserved noncoding elements (CNEs). A functional assay using zebrafish has shown that most of the CNEs have reproducible and specific enhancer activity. This enhancer activity is often detected in a subset of tissues which reflect the endogenous expression pattern of a proximal gene, though some CNEs may act over a long range. We propose that the distribution of CNEs, and their probable association with a number of genes throughout the region, imposes a critical constraint on genome architecture, resulting in the maintenance of such a large section of conserved synteny across the vertebrate lineage.

Animals↗

PubMed2006

The conserved tyrosine residues 401 and 1044 in ATP sites of human P-glycoprotein are critical for ATP binding and hydrolysis: evidence for a conserved subdomain, the A-loop in the ATP-binding cassette.

Each nucleotide-binding domain (NBD) of mammalian P-glycoproteins (Pgps) and human ATP-binding cassette (ABC) B subfamily members contains a tyrosine residue approximately 25 residues upstream of the Walker A domain. To assess the role of the conserved Y401 and Y1044 residues of human Pgp, we substituted these residues with F, W, C, or A either singly or together. The mutant proteins were expressed in a Vaccinia virus-based transient expression system as well as in baculovirus-infected HighFive insect cells. The Y401F, Y401W, Y1044F, Y1044W, or Y401F/Y1004F mutants transported fluorescent substrates similar to the wild-type protein. On the other hand, Y401L and Y401C exhibited partial (30-50%) function, and transport was completely abolished in Y401A, Y1044A, and Y401A/Y1044A mutant Pgps. Similarly, in Y401A, Y1044A, and Y401A/Y1044A mutants, TNP-ATP binding, vanadate-induced trapping of nucleotide, and ATP hydrolysis were completely abolished. Thus, an aromatic residue upstream of the Walker A motif in ABC transporters is critical for binding of ATP. Additionally, the crystal structures of several NBDs in the nucleotide-bound form, data mining, and alignment of 18,514 ABC domains with the consensus conserved sequence in a database of all nonredundant proteins indicate that an aromatic residue is highly conserved in approximately 85% of ABC proteins. Although the role of this aromatic residue has previously been studied in a few ABC proteins, we provide evidence for a near-universal structural and functional role for this residue and recognize its presence as a conserved subdomain approximately 25 amino acids upstream of the Walker A motif that is critical for ATP binding. We named this subdomain the "A-loop" (aromatic residue interacting with the adenine ring of ATP).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Conserved and non-conserved regions in the Sendai virus genome: evolution of a gene possessing overlapping reading frames.

We have sequenced the entire genome of a virulent field isolate of Sendai virus, the Hamamatsu strain, and compared the sequence with that of a distant related strain, the Z strain. Calculation of synonymous and non-synonymous (amino acid changing) nucleotide substitutions revealed regions where changes were permissive and non-permissive, and the experimentally determined functional region were found to be conserved, showing that important regions for function were conserved during evolution. In the cistron-overlapping regions in the P gene, one reading frame was conserved, whereas the other overlapping frame was flexible. The priority of one frame could be a strategy for evolution of an overlapping gene of RNA viruses. We found that the carboxyl two thirds of the C protein was conserved over the amino-terminal one third, possessing priority to the overlapping P polypeptide. This suggests that the carboxyl two thirds of the C protein have a functional importance. We also found a highly variable region between the L coding frame and the 5' trailer sequence. The relevance of these findings to actual viral replication should be clarified in the future.

Base Sequence↗

PubMed1995

[Studies on theory and models of systemic conservation of animal and poultry genetic resources. I. Theory analysis of systemic conservation of animal and poultry genetic resources].

The concept and fundamentals of Systemic Conservation of Animal and Poultry Genetics Resources (SCAPGR) and mathematical models of genetic structure with conservation population were proposed. The SCAPGR regarded all genes of a given species in definite time and space as conservation object and live animal preservation combining with modern biotechnology as basic method. The SCAPGR might systematically conserve genes controlling the characters of a given species as well as regional varieties. In a no overlapping generation population with selection, mutation migration and random drift under consideration, two mathematical models presented in this paper might describe change of frequencies of multiple alleles at a locus and population mean of metrical characters resp.

Animals↗

PubMed1988

The complete nucleotide sequence of the outer coat protein, VP5, of the Australian bluetongue virus (BTV) serotype 1 reveals conserved and non-conserved sequences.

The complete sequence of the outer coat protein, VP5, of the Australian BTV serotype 1 was determined and found to be 1634 nucleotides in length. One single open reading frame of 526 amino acids was observed defining a protein of Mr 59,252 and having a charge of +0.5 at neutral pH. When compared to VP5 of BTV serotype 10 from the United States of America (US) (Purdy et al., 1986, J. Gen. Virol. 67, 957) a homology of 68% at the nucleotide level and 76% at the amino acid level, was observed. However, this conservation at the protein level was more apparent in certain regions of the gene. In four main regions the conservation varied from 83-91% while in the remaining regions the homology dropped to between 56-62%. Many of the amino acid substitutions were conservative in nature, raising the apparent overall homology to 87%. Comparisons of the hydropathy profiles of the two proteins again revealed a remarkable degree of conservation. The importance of these observations is discussed.

Amino Acid Sequence↗

PubMed1992

Nucleotide sequence of the capsid protein gene of two serotypes of San Miguel sea lion virus: identification of conserved and non-conserved amino acid sequences among calicivirus capsid proteins.

The San Miguel sea lion viruses, members of the calicivirus family, are closely related to the vesicular disease of swine viruses which can cause severe disease in swine. In order to begin the molecular characterization of these viruses, the nucleotide sequence of the capsid protein gene of two San Miguel sea lion viruses (SMSV), serotypes 1 and 4, was determined. The coding sequences for the capsid precursor protein were located within the 3' terminal 2620 bases of the genomic RNAs of both viruses. The encoded capsid precursor proteins were 79,500 and 77,634 Da for SMSV 1 and SMSV 4, respectively. The SMSV 1 protein was 47.7% and SMSV 4 was 48.6% homologous to the feline calicivirus (FCV) capsid precursor protein while the two SMSV capsid precursors were 73% homologous to each other. Six distinct regions within the capsid precursors (denoted as regions A-F) were identified based on amino acid sequence alignment analysis of the two SMSV serotypes with FCV and the rabbit hemorrhagic disease virus (RHDV) capsid protein. Three regions showed similarity among all four viruses (regions B, D and F) and one region showed a very high degree of homology between the SMSV serotypes but only limited similarity with FCV (region A). RHDV contained only a truncated region A. A fifth region, consisting of approximately 100 residues, was not conserved among any of the viruses (region E) and, in SMSV, may contain the serotype-specific determinants. Another small region (region C) contained between 15 and 27 amino acids and showed little sequence conservation. Region B showed the highest degree of conservation among the four viruses and contained the residues which had homology to the picornavirus VP3 structural protein. An open reading frame, found in the 3' terminal 514 bases of the SMSV genomes, encoded small proteins (12,575 and 12,522 Da, respectively for SMSV 1 and SMSV 4) of which 32% of the conserved amino acids were basic residues, implying a possible nucleic acid-binding function.

Amino Acid Sequence↗

PubMed1998

Invasive versus conservative strategies in unstable angina and non-Q-wave myocardial infarction following treatment with tirofiban: rationale and study design of the international TACTICS-TIMI 18 Trial. Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy. Thrombolysis In Myocardial Infarction.

In the management of unstable angina and non-Q-wave acute myocardial infarction (AMI), there is considerable debate regarding the use of invasive strategy versus conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B trial found similar clinical outcomes for the 2 strategies, but the Veterans Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher mortality with the invasive strategy. Both these trials were conducted before platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which improve clinical outcome. Thus, there is a need to reexamine the question of which management strategy is optimal in the current era of platelet glycoprotein IIb/IIIa inhibition and new coronary interventions. The Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS-TIMI 18) trial is an international, multicenter, randomized trial that is evaluating the clinical efficacy of early invasive and early conservative treatment strategies in patients with unstable angina or non-Q-wave AMI treated with tirofiban, heparin, and aspirin. Patients are randomized to an invasive strategy, involving cardiac catheterization within 4 to 48 hours and revascularization with angioplasty or bypass surgery if feasible, versus a conservative strategy, where patients are referred for catheterization only for recurrent pain at rest or provokable ischemia. The primary end point is death, MI, or rehospitalization for acute coronary syndromes through a 6-month follow-up. The trial is also testing the "troponin hypothesis," that baseline troponins T and I will be useful in selecting an optimal management strategy.

Adolescent↗

PubMed1998

[The organ-conserving treatment of early carcinoma of the breast. I. The biological, histological and radiobiological bases. II. Radiotherapy--an essential component in the organ-conserving surgery of early carcinoma of the breast].

One of the major achievements in the last 20 years is the awareness that mutilating surgery--mastectomy--is a biologically obsolete therapeutic approach, and no longer indicated in the treatment of early breast cancer which in turn, has a dramatic effect insofar as mammary gland preservation is obviously an important consideration for each woman. Either of the operative procedures--quadrantectomy and lumpectomy--should be by all means followed by radiotherapy with a view to control local recurrences of the process. Clinical trials covering borderline disciplines assay the contribution of the answers to a number of questions, as follows: 1) Is the effect of conservative mammary gland treatment comparable to that of mastectomy? 2) Is radiotherapy an essential component of conservative breast surgery? 3) Is conservative surgery indicated in all cases presenting early breast carcinoma? 4) Which are the factors exerting influence on the conservative therapeutic approach to breast cancer?

Breast↗

PubMed2001

Position of the American Dietetic Association: dietetics professionals can implement practices to conserve natural resources and protect the environment. (Previously titled "natural resource conservation and waste management").

It is the position of the American Dietetic Association to encourage environmentally responsible practices that conserve natural resources, minimize the quantity of waste that is generated, and have the least adverse affect on the health of all living organisms and the environment. All components of the food system, from farmer to consumer, are affected by the availability and cost of energy and the availability and quality of water. Outdoor and indoor air quality significantly impacts the health of all living organisms. Decisions that dietetics professionals make as practitioners and consumers can affect the quantity and type of solid waste generated. The demand for natural resources should be evaluated when selecting the most cost-effective, environmentally sensitive approach to the management of solid waste. Special precautions are needed when using and disposing of hazardous and medical waste to protect the safety of our clients and employees. This position paper provides information and resources for dietetics professionals for addressing the complexity of the environmental issue presented. Conservation strategies are identified that dietetics professionals can use in their worksites and at home. These conservation practices may reduce cost and decrease the environmental impact we have on our communities and the world.

Air Pollution↗

PubMed2002

Analysis of conserved and non-conserved amino acids critical for ALSV (Avian leukemia and sarcoma viruses) integrase functions in vitro.

Retroviral integrase (IN) is the viral enzyme responsible for the integration of viral DNA into host cellular DNA. In vitro, recombinant IN protein is able to catalyze the 3'-processing, strand transfer and disintegration activities. In order to analyze the importance of specific residues of ALSV (Avian leukemia and sarcoma viruses) IN protein, we introduced 31 amino acid substitutions either in residues previously shown by others to be involved in IN oligomerization or in selected conserved and non-conserved residues through the IN sequence. We tested, in vitro, the three catalytic activities of these mutants as well as their capacity to bind DNA. We found that (i) 88% of the substitutions occurring on well-conserved residues have an effect on IN activities (ii) two mutants (S85T in the central catalytic domain and N197C in the C-terminal domain) present a reduced efficiency of DNA binding compared to the wild type protein. Moreover, all mutations made on the dimer interface of C-terminal domain present reduced activities, suggesting an important role of this part of the protein. Finally, for some mutations, we observed differences between the ALSV and HIV (Human immunodeficiency virus) IN corresponding residues.

Alpharetrovirus↗

PubMed2002

Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function.

A majority (84%) of G protein-coupled receptors have a proline (P5.50) in the middle of the fifth transmembrane domain. However, one of the unique structural features of cannabinoid receptors is the replacement of the conserved P5.50 by a leucine (L5.50). It has been shown that a conserved tyrosine (Y5.58), located at the cytoplasmic side of P5.50, is crucial for the signal transduction of several G protein-coupled receptors. We proposed that the replacement of P5.50 by L5.50 and the presence of the conserved Y5.58 in this context are important for the function of CB2. Mutating L5.50 to a proline abolished ligand binding, whereas mutating Y5.58 to an alanine resulted in a rightward shift of the competition binding curves. Both of these mutations led to a complete loss of the ability of cannabinoid agonists to inhibit forskolin-stimulated cAMP accumulation.

Amino Acid Sequence↗