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PubMed1987

Structural variations in the alanine-rich antifreeze proteins of the pleuronectinae.

The sequence and activity of antifreeze proteins from two right eye flounder species were compared to assess the influence of structural variations on antifreeze capacity. The cDNA encoding the major serum antifreeze protein in the yellowtail flounder (Limanda ferruginea) was cloned from liver tissue. Its DNA sequence shows that the precursor to the antifreeze is a 97-residue preproportion. Edman degradation identified the N-terminus of the 48-amino-acid mature serum antifreeze protein and confirmed the sequence of the first 36 residues. A comparison with the previously determined winter flounder antifreeze protein and mRNA sequences shows strong homology through the 5' and 3' untranslated regions and in the peptide region. The mature protein section has the greatest sequence variation. Specifically, the yellowtail antifreeze protein, in contrast to that of the winter flounder, contains a fourth 11-amino-acid repeat and lacks several of the hydrophilic residues that have been postulated to aid in the binding of the protein to ice crystals. Intramolecular salt bridges are present in the antifreeze proteins from both species but in different registries with respect to the 11-amino-acid repeats. On a mass basis the yellowtail flounder antifreeze, though longer than that of the winter flounder, is only 80% as effective at depressing the freezing temperature of aqueous solutions. This lower activity might be due to the reduced number of hydrophilic ice-binding residues per molecule.

Alanine↗
PubMed1996

Conformational heterogeneity in two regions of TAT results in structural variations of this protein as a function of HIV-1 isolates.

TAT protein is an essential regulatory protein of the human immunodeficiency virus type 1 (HIV-1). Inhibition of TAT activity blocks the virus cycle, and a drug that blocks TAT is one of the possibilities to cure AIDS. Circular dichroism (CD) was measured for TAT peptides covering the TAT sequence with overlaps. The CD spectrum of each peptide was measured in different solvents to evaluate the ability of each TAT region to form different secondary structures. The most variation or conformational heterogeneity is observed with the two regions adjacent to the TAT basic region. CD data show that the basic region can adopt an extended structure in a full TAT protein, which is not the case for the isolated peptide. TAT sequences from the different HIV-1 isolates were analyzed, and the results showed that the sequences could be gathered into six groups. Molecular modeling was done on the various isolates based on a TAT structure from two-dimensional NMR. After minimization and dynamic steps, the modeled three-dimensional structures were compared. The results showed structural variations of the TAT protein as a function of the HIV-1 isolates. These structural variations were mainly in the two regions adjacent to the basic region, confirming the conformational heterogeneity indicated by the CD measurements. Furthermore, Chou-Fasman analysis shows significant changes in propensities for each secondary structure only for regions III and V. This conformational heterogeneity should be essential for TAT activity and points out that regions III and V are a poor potential target to design a TAT ligand. We propose a target involving TAT structurally conserved regions, accessible whatever the size of the TAT C terminus.

Amino Acid Sequence↗
PubMed1983

Evidence for minor structural variations of class II genes in wild and inbred mice.

We organized 29 B10.W lines into eight antigenic groups on the basis of similarities in the antigenic phenotypes of their class II antigens. Tryptic peptide fingerprint comparisons of class II antigens in different antigenic groups detected structural variations in 30 to 60% of the tryptic peptides. In contrast, less than 10% of the tryptic peptides were distinguishable in comparisons of class II antigens within the same antigenic group. These results suggest structurally discrete allelic families of class II genes exist in wild mouse populations.

Animals↗
PubMed1986

Demonstration of structural variation in rat incisor dentin as determined by the x-ray Laue method.

Rat incisor dentin was studied by an x-ray micro-Laue method to investigate the relationship between crystal orientation and structural variation in the dentin. The results showed that crystal orientation was very poor in the labial dentin, but that the crystals were well-oriented in the lingual dentin. In the lingual dentin, the axis of crystal orientation was parallel to the tooth axis. It is suggested that the difference in crystal orientation between the lingual and labial dentin is due to the different mode of calcification between the two.

Animals↗
PubMed1983

Sequence-dependent structural variations in two right-handed alternating pyrimidine-purine DNA oligomers in solution determined by nuclear Overhauser enhancement measurements.

A 500 MHz 1H-n.m.r. study on two right-handed self-complementary double-stranded alternating pyrimidine-purine oligodeoxyribonucleotides, 5'dCGTACG and 5'dACGCGCGT, is presented. Using the proton-proton nuclear Overhauser effect, proton resonances are assigned by a sequential method and a large number of interproton distances, both intra- and internucleotide, are determined (113 for 5'dCGTACG and 79 for 5'dACGCGCGT). The general procedure required to solve the three-dimensional solution structures of oligonucleotides from such distance data is outlined and applied to these two oligonucleotides. In the case of both oligonucleotides the overall solution structure is that of B DNA, namely a right-handed helix with a helical rise of approximately 3.3 A, 10 bp per turn and the base pairs approximately perpendicular to the helix axis. In the case of 5'dCGTACG, subtle local structural variations associated with the pyrimidine and purine nucleotides are superimposed on the overall structure but the mononucleotide repeating unit is preserved. In contrast, 5'dACGCGCGT has a clear alternating structure with a dinucleotide repeat, alternation occurring in the local helical twist and the glycosidic bond, sugar pucker and phosphodiester backbone conformations.

DNA↗
PubMed1991

Swimming navigation and structural variations of the infrapyramidal mossy fibers in the hippocampus of the mouse.

The extent of the infrapyramidal mossy fiber projection in CA3 (IIP-MF) at the midseptotemporal level correlates negatively with two-way avoidance learning and positively with performance in the radial maze, both tasks known to be sensitive to hippocampal lesions. If hippocampal structural variations are causing behavioral variations, one must predict positive correlations between the extent of the IIP-MF and performance in swimming navigation. Thus, the authors studied learning and reversal learning of swimming navigation in mice in which the size of the IIP-MF had been randomized by means of systematic crosses and in 2 mouse strains known for differential infrapyramidal projections (C57BL/6 and DBA/2). In 19 random-bred mice (9 male, 10 female), the extent of the IIP-MF showed negative correlations with swimming time after platform reversal (day 4: r = -0.50, P < .03; day 5 r = -0.73, P < .001), but none during acquisition of the task. In addition, statistical analysis suggested an influence of asymmetrically distributed mossy fiber projections during reversal learning. The strain comparison between 18 DBA/2 and 16 C57BL/6 male mice confirmed these results: no strain difference during days 1-3, and a significantly faster swimming time in the strain C57BL/6 (with large IIP-MF) at day 5 (second day of reversal), associated with significantly more crossings of the former platform location during the early phases of reversal learning. This latter measure was also negatively correlated with asymmetry of the IIP-MF in both strains. Finally, variations of the IIP-MF were correlated partially with adjustment of swimming speed that appeared to depend on size and asymmetry of CA4 as well. Thus, natural variations in the size of the IIP-MF distribution, and, perhaps, of CA4, appear to linearly influence processes directly involved in complex spatial learning.

Animals↗
PubMed1966

Immunoglobulin structure: variation in the sequence of Bence Jones proteins.

Analysis of the amino acid sequence of one Bence Jones protein is almost comtplete. Many points of interchange occur in the amino terminal. portion of the molecule relative to partial-sequence data for other proteins. Most, but not all, are, compartible with one-step mutations. Such structural variation in immunoglobulin light chains may result from many related genes.

Amino Acid Sequence↗
PubMed2026

Complex structural variation, phylogeny, and disease associations of the mucin pangenome.

Mucins are large glycoproteins that provide hydration and barrier function to epithelial tissues. Although genetically heterogeneous, all mucins harbor a large exon composed of variable number tandem repeats (VNTRs). Short-read sequencing has limited our understanding of mucin VNTR diversity and makes disease association studies challenging. We leverage 296 long-read phased genome assemblies to characterize 14 mucin family members, achieving &#x2265;97% accuracy across 572 haplotypes. Phylogenetic haplogroup analysis reveals extraordinary structural heterozygosity, with MUC4 harboring the greatest allelic diversity (n=240 distinct lengths) and MUC12 the greatest size range (&#x394; = 55,233 bp; 23,080 amino acids). Ten mucins show significant population stratification (pFDR < 0.05). At the MUC4/MUC20 locus, we characterize higher-order structural variation, including a recurrent inversion, copy number variation, and interlocus gene conversion. Optimized genotyping achieves &#x2265;95% haplogroup concordance across 10 loci. We apply this to 4,637 deeply phenotyped cystic fibrosis patients and identify a significant association between short MUC1 VNTRs and severe disease (p=0.0056), demonstrating the pangenome's utility for complex locus genotyping and disease discovery.

Journal Article↗
PubMed2026

Pan-genome-based resequencing of 2,320 accessions reveals structural variations and accelerates breeding advances in cultivated peanut.

The cultivated peanut is a crucial global legume crop that is essential for food security and nutrition, particularly in developing regions. However, its limited genetic variation hampers breeding progress and yield improvement. Here we constructed a graph-based pan-genome for peanut, incorporating 14 genomes that represent all 6 peanut varieties. Using this pan-genome, we genotyped 2,320 accessions, covering 88.03% of ICRISAT and 59.21% of USDA core germplasm, enriching valuable resources for genomic studies and breeding. We cataloged genomic structural variations and investigated the role of homoeologous exchanges in population divergence. Through our pan-genome approach, we overcame the challenges of genotyping posed by homoeologous exchanges and identified key genes associated with flowering and dwarfism in peanut. By integrating superior haplotypes and germplasm resources guided by the pan-genome, we further developed high-yield dwarf lines. This work provides essential genomic resources to accelerate functional gene discovery and modern peanut breeding.

Journal Article↗
PubMed2025

Substantial non-homologous recombination and structural variation results from Brassica AABC and CCAB hybrid meiosis.

Meiotic crossovers contribute to genetic diversity and play a crucial role in homologous chromosome segregation. Non-homologous crossovers in Brassica, involving the exchange of genetic material between genomes, can be valuable for transferring novel traits or characteristics between Brassica species. However, there are a limited number of studies that specifically investigate crossover frequencies in populations of interspecific hybrids. We investigated the distribution and frequency of homologous crossover events, as well as non-homologous recombination and structural variation, in hybrids between B. juncea (AABB)&#x2009;&#xd7;&#x2009;B. napus (AACC) (resulting in AABC hybrids; 5 genotypes) and B. napus (AACC)&#x2009;&#xd7;&#x2009;B. carinata (BBCC) (resulting in CCAB hybrids; 4 genotypes). The analysis was performed on individuals derived from microspore culture of both unreduced and reduced gametes produced by the AABC and CCAB hybrids. All AABC and almost all CCAB unreduced gamete-derived individuals and most AABC and CCAB reduced gamete-derived individuals showed copy number variation indicative of non-homologous (A-C) recombination. Additionally, a higher frequency of homologous crossovers, also in centromeric and pericentromic regions, was observed in the diploid genomes of the AABC and CCAB hybrids. Overall, these hybrid types show high frequencies of A-C introgressions, which may be useful in B. juncea or B. carinata introgression breeding, and this increased recombination frequency may help break up existing linkage disequilibrium blocks in the Brassica A and C genomes.

Meiosis↗
PubMed1984

DNA structural variations produced by actinomycin and distamycin as revealed by DNAase I footprinting.

The technique of DNAase I footprinting has been used to investigate preferred binding sites for actinomycin D and distamycin on a 160-base-pair DNA fragment from E. coli containing the tyr T promoter sequence. Only sites containing the dinucleotide step GpC are protected by binding of actinomycin, and all such sites are protected. Distamycin recognizes four major regions rich in A + T residues. Both antibiotics induce enhanced rates of cleavage at certain regions flanking their binding sites. These effects are not restricted to any particular base sequence since they are produced in runs of A and T by actinomycin and in GC-rich sequences by distamycin. The observed increases in susceptibility to nuclease attack are attributed to DNA structural variations induced in the vicinity of the ligand binding site, most probably involving changes in the width of the helical minor groove.

Base Sequence↗
PubMed1988

The central projections of the stretch receptor neurons of crayfish: structure, variation, and postembryonic growth.

Each stretch receptor neuron (SR) of the crayfish abdomen projects from its peripherally located soma an axon that enters the CNS through the second nerve (N2) of its segmental ganglion. Co2+ backfills of N2 revealed that this axon bifurcates, sending one branch to the brain and the other to the terminal abdominal ganglion. Each axon makes many short lateral branches as it traverses each of the other segmental ganglia, and has 2 major arborizations--one in the tritocerebrum of the brain and the other in the terminal abdominal ganglion, G6. These projections to G6 are described in detail. Individual SR axons from different segments were impaled in G6 with a Lucifer yellow-filled microelectrode, identified physiologically, and then filled to discover their structures. In a sample of more than 50 SR neurons, no systematic structural differences between the projections of phasic SR neurons and tonic SR neurons were observed. Three kinds of structural variability occurred in these projections to G6: unusual primary axon shape, long primary axon, and large terminal varicosities. Comparisons of SR neurons that originated in different segments revealed a segmental gradient in the probability of each structural variant. SR neurons from more anterior segments were more likely to show these structural variations. Comparisons of these variations in crayfish of different sizes showed that unusual primary axon shape and long primary axons were more probable in large crayfish than in small ones. Therefore, these variations are probably the products of postembryonic growth of the nervous system.

Animals↗
PubMed1987

Evidence for diverse structural variations of the forms of human FSH within and between pituitaries.

The biological activity of FSH in vitro (B-vitro) was compared with its radioimmunological (RIA) activity in 38 pituitary extracts from men and women. The B-vitro method was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10-day-old rats. The mean B-vitro/RIA ratios for FSH of men and young and elderly women were almost identical. The mean values of median charge of the forms of FSH differed significantly between the three groups of human adults. The B-vitro/RIA ratio of different forms of FSH, separated by electrophoresis of 14 individual pituitary extracts, was higher for less negatively charged than for more negatively charged forms. Some forms of FSH with the same charge and separated from different pituitary extracts, e.g. from a young and an elderly woman, had significantly different B-vitro/RIA ratios. This ratio, thus, was not related to the charge per se of the hormone. However, the relation between the B-vitro/RIA ratio and the charge of FSH was similar for individual pituitary extracts when charge was expressed in relation to median charge. The results suggest that different molecular structural variations of FSH are involved in the polymorphisms observed within and between individual pituitaries. In human adults, the variation of FSH between the pituitaries mainly affects the metabolic clearance rate (MCR) of the hormone, whereas the variation within the individual pituitary affects both the MCR of the hormone and its biological effect at the target cell.

Adolescent↗
PubMed1988

Genetic studies of low abundance human plasma proteins. VIII. Inherited structural variation in antithrombin III.

Genetically determined structural polymorphism of antithrombin III has been observed using ultra narrow pH polyacrylamide isoelectric focusing gels, followed by immunoblotting. The products of three alleles at the antithrombin III structural locus have been detected in normal U.S. white and black blood donors. The frequencies of the three alleles, AT III* 1, AT III* 2 and AT III* 3, respectively, are: 0.878, 0.103, 0.019 in whites and 0.916, 0.068, 0.016 in blacks. Family data from a large number of families establish an autosomal codominant pattern of inheritance of the three alleles.

Alleles↗
PubMed1991

Structural variation and (+)-amphetamine-like discriminative stimulus properties.

Rats were trained to discriminate (+)-amphetamine sulfate (5.43 mumol/kg, 1 mg/kg) from saline in a food-reinforced, two-lever drug discrimination paradigm. Side chain variations of the amphetamine molecular structure were analyzed for their effects on the discriminative stimulus properties of this prototype central nervous system stimulant. Partial generalization was observed for the alpha-ethyl homologue of (+)-amphetamine, (+)-AEPEA, and for 2-aminoindan (AI), while 5,6-methylenedioxy-2-aminoindan (MDAI) elicited only saline-appropriate responding. By contrast, 2-amino-1,2-dihydronaphthalene (ADN) and 2-aminotetralin (AT) completely substituted for (+)-amphetamine. Relative to the training drug, ADN was 1/4 as potent and AT was 1/8 as potent. The S-(-)-isomer of ADN was found to be responsible for the (+)-amphetamine-like discriminative properties of the racemate. The results suggest that constraining or extending the alpha-alkyl substituent of (+)-amphetamine has a deleterious effect on the ability of the resulting analogue to adopt the active conformation of (+)-amphetamine, thereby diminishing its characteristic discriminative stimulus properties.

Animals↗
PubMed1999

High resolution solution structure of apo calcyclin and structural variations in the S100 family of calcium-binding proteins.

The three-dimensional solution structure of apo rabbit lung calcyclin has been refined to high resolution through the use of heteronuclear NMR spectroscopy and 13C, 15N-enriched protein. Upon completing the assignment of virtually all of the 15N, 13C and 1H NMR resonances, the solution structure was determined from a combination of 2814 NOE-derived distance constraints, and 272 torsion angle constraints derived from scalar couplings. A large number of critical inter-subunit NOEs (386) were identified from 13C-select, 13C-filtered NOESY experiments, providing a highly accurate dimer interface. The combination of distance geometry and restrained molecular dynamics calculations yielded structures with excellent agreement with the experimental data and high precision (rmsd from the mean for the backbone atoms in the eight helices: 0.33 A). Calcyclin exhibits a symmetric dimeric fold of two identical 90 amino acid subunits, characteristic of the S100 subfamily of EF-hand Ca(2+)-binding proteins. The structure reveals a readily identified pair of putative sites for binding of Zn2+. In order to accurately determine the structural features that differentiate the various S100 proteins, distance difference matrices and contact maps were calculated for the NMR structural ensembles of apo calcyclin and rat and bovine S100B. These data show that the most significant variations among the structures are in the positioning of helix III and in loops, the regions with least sequence similarity. Inter-helical angles and distance differences for the proteins show that the positioning of helix III of calcyclin is most similar to that of bovine S100B, but that the helix interfaces are more closely packed in calcyclin than in either S100B structure. Surprisingly large differences were found in the positioning of helix III in the two S100B structures, despite there being only four non-identical residues, suggesting that one or both of the S100B structures requires further refinement.

Animals↗