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Query: UNIPROT:P06889 (Mol)
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The genes coding for hsp 16-48, previously identified by cDNA cloning, and for another 16-kilodalton heat shock protein designated hsp16-1 were characterized by DNA sequencing. The two genes were arranged in a head-to-head orientation. Both the coding and flanking regions were located within a 1.9-kilobase module which was duplicated exactly to form a 3.8-kilobase inverted repeat structure. The inverted repeat structure ended in an unusual guanine-plus-cytosine-rich sequence 24 nucleotides in length. The identity of the two modules at the nucleotide sequence level implies that the duplication event may have occurred recently. Alternatively, gene conversion between the two modules could also maintain homology of the two gene pairs. The small heat shock genes of Caenorhabditis elegans contained TATA boxes and heat-inducible promoters, the latter agreeing closely with the Drosophila melanogaster consensus sequence described by Pelham (Cell 30:517-528, 1982). Unlike the homologous D. melanogaster genes, each of these C. elegans genes contained a short intron, the position of which has been conserved in a related murine alpha-crystallin gene. The intron separated variable and conserved regions within the amino acid sequences of the encoded heat shock polypeptides.
Mol Cell Biol 1985 Jun
PMID:Locus encoding a family of small heat shock genes in Caenorhabditis elegans: two genes duplicated to form a 3.8-kilobase inverted repeat. 403 52

We have characterized five human gamma-crystallin genes isolated from a genomic phage library. DNA sequencing of four of the genes revealed that two of them predict polypeptides of 174 residues showing 71% homology in their amino acid sequence; the other two correspond to closely related pseudogenes which contain the same in-frame termination codon at identical positions in the coding sequence. Two of the genes and one of the pseudogenes are oriented in a head-to-tail fashion clustered within 22.5 kilobases. All three contain a TATA box 60 to 80 base pairs upstream of the initiation codon and a highly conserved segment of 44 base pairs in length immediately preceding the TATA box. The two genes and the two pseudogenes are similar in structure: each contains a small 5' exon encoding three amino acids followed by two larger exons that correspond exactly to the two similar structural domains of the polypeptide. The first intron varies from 100 to 110 base pairs, and the second intron ranges from 1 to several kilobases, rendering an overall gene size of 1.7 to 4.5 kilobases. At least one of the two pseudogenes appears to have been functional before inactivation, suggesting that their identical mutation was generated by gene conversion.
Mol Cell Biol 1985 Jun
PMID:Structural and evolutionary relationships among five members of the human gamma-crystallin gene family. 403 58

The eye lens contains a structural protein, alpha crystallin, composed of two homologous primary gene products alpha A2 and alpha B2. In certain rodents, still another alpha crystallin polypeptide, alpha AIns, occurs, which is identical to alpha A2 except that it contains an insertion peptide between residues 63 and 64. In this paper we describe the complete alpha A crystallin gene that has been cloned from DNA isolated from Syrian golden hamster. Evidence is provided that the alpha A gene is present as a single copy in the hamster genome. The detailed organization of the gene has been established by means of DNA sequence analysis and S1 nuclease mapping, revealing that the gene consists of four exons. The first exon contains the information for the 68 base-pair long 5' non-coding region as well as the coding information for the first 63 amino acids. The second exon encodes the 23 amino acid insertion sequence, the third exon codes for amino acid 87 to 127 of the alpha AIns chain, whereas the last exon encodes the C-terminal 69 amino acids and contains the information for the 523 base-pair long 3' non-coding region. The second exon is bordered by a 3' splice junction (A X G/G X C), which deviates from the consensus for donor splice sites (A X G/G X T). This deviation is found in both hamster and mouse. An internal duplication was detected in the first exon by using a DIAGON-generated matrix for comparison. By means of similar DIAGON-generated matrices it was confirmed that the amino acids coded for by the third and fourth exons are homologous to the small heat-shock proteins of Drosophila, Caenorhabditis and soyabean. The implications of the differential splicing and the evolutionary aspects of the detected homologies are discussed.
J Mol Biol 1985 Sep 20
PMID:Complete structure of the hamster alpha A crystallin gene. Reflection of an evolutionary history by means of exon shuffling. 405 47

The present studies were based on the premise that any common determinants in homologous proteins must have originated with the common ancestor of all of the taxonomic groups in which that determinant occurs. Cross-reacting antigenic determinants of lens alpha crystallin various classes of modern vertebrates were used to trace their evolutionary relationships. For quantitation of evolutionarily distinct determinants, equimolar amounts of alpha crystallin or its subunits, in either monomeric or reaggregated form, were bound to a matrix, then saturated with 125I-labeled Fab fragments of anti-cattle alpha crystallin antibodies having phylogenetically restricted specificities. This quantitative procedure has the important advantage of independence from variation in antibody responses to different determinants of the same antigenic molecule. The procedure is not impaired by steric hindrance. Both the SH-containing and SH-free subunits of cattle lens alpha crystallin were found to contain common antigenic determinants with the cyclostomata alpha crystallin. Such determinants originatd in evolution with the first vertebrates, the primitive agnatha. Antigenic determinants transferred from ancestral aquatic and land vertebrates to the mammals were found to constitute 93% of all determinants reactive in the monomeric SH-free subunits of cattle alpha crystallin. These determinants constitute only 76.5% of all determinants which are reactive in the SH-containing subunits. The antigenic determinants on both types of subunits were all found to be different. These findings indicate that evolutionary changes must have occurred more slowly in SH-free subunits than in SH-containing subunits. Significant decreases or increases were found in the content of various evolutionarily distinct determinants reactive in the reaggregated subunits as compared to the ones reactive in monomeric subunits. These differences can result from the formation of new conformational antigenic determinants during aggregation as well as from the burial or exposure of other determinants after aggregation. Different amounts of evolutionarily distinct antigenic determinants were found to be reactive in the molecules dissociated into subunits than in the intact molecules one of the reasons being that the intact molecules contain phylogenetically distinct determinants which depend on the quaternary structure of the protein molecule. The data obtained indicate that the quaternary structure of cattle alpha crystallin has, to a large degree, remained unchanged since the origin of vertebrates.
J Mol Evol 1980 Jul
PMID:Molecular evolution and subunit structure of cattle lens alpha crystallin. 615 29

Two complementary DNA clones pRL gamma-2 and pRL gamma-3 of different rat lens gamma-crystallin messenger RNAs have been used to identify gamma-crystallin gene sequences in rat genomic DNA. Subsequently, the DNA present in the 18,000 to 20,000 bases region of the EcoRI digest, giving rise to a strong doublet hybridization signal, was cloned in lambda phage Charon-4A. One of the clones, lambda RCH gamma-3, carrying an insert of 17,500 bases has been characterized in detail. From analysis at the restriction enzyme level with 5'-, "middle" and 3'-specific subprobes of pRL gamma-3 it could be deduced that lambda RCH gamma-3 contains only one gamma-crystallin gene. The coding sequences of this gene are interrupted by intronic DNA. The primary structure of this gene and its flanking regions have been established by sequencing the relevant regions of a subclone of lambda RCH gamma-3, designated pRCH gamma-3 . 1. The sequence data show that the gamma-crystallin gene extends over 2700 bases of rat genomic DNA. The gene is split by two introns, one of 87 base-pairs after the third translation codon and a large one of 1880 base-pairs after codon 84. The mosaic structure of the gene is strictly co-linear with the structure of the gamma-crystallin polypeptide in that the large intron is positioned in a region which specifies the so-called "connecting peptide" and which links the two highly symmetrical and homologous protein domains. Although expected from the cDNA and protein sequence no introns were observed between the coding regions in the DNA specifying the two homologous folding motifs present in each protein domain. The relevance of this phenomenon in terms of the evolution of the mature gamma-crystallin gene is discussed.
J Mol Biol 1983 Dec 25
PMID:Strict co-linearity of genetic and protein folding domains in an intragenically duplicated rat lens gamma-crystallin gene. 631 7

delta-Crystallin is a major structural protein of avian and reptilian lenses that is absent from the lenses of fish, amphibia and mammals. It appears to be a tetrameric protein with a native molecular weight near 200 000 (200K) and polypeptide molecular weight near 50K and 48K) (see Note added in proof). The alpha-crystallin polypeptides are extremely similar, associate in various combinations of four and are held together by hydrophobic interactions. Although principally cytoplasmic, delta-crystallin may associate with the cell membrane. delta-Crystallin differs from other lens crystallins in its alpha-helical content, native and subunit molecular weights, antigenicity, low wavelength of maximum fluorescence emission (315 nm) after excitation at 280 nm and amino acid composition (high in leucine; low in aromatic residues en no cysteine). Analyses of peptides, native and subunit molecular weights, and circular dichroism spectra indicate that the primary, secondary, tertiary and subunit structures of delta-crystallin have been generally conserved during evolution. There are at least two tandemly arranged delta-crystallin containing 13-15 introns in the chicken; a similar structure exists for a cloned delta-crystallin gene in the duck. Experiments with chicken show that delta-crystallin synthesis occurs principally in the embryo, especially during lens fiber cell differentiation. delta-Crystallin synthesis also takes place during lens fiber cell differentiation in culture. There is evidence for both transcriptional and post-transcriptional regulation of delta-crystallin synthesis. Current studies on the crystallographic and primary structures of delta-crystallin, on the structure, evolution and expression of the delta-crystallin genes, and on the translation of delta-crystallin mRNAs make this specialized lens protein an active area of investigation.
Mol Cell Biochem 1984
PMID:Delta crystallins and their nucleic acids. 636 10

A library of recombinant plasmids carrying complementary DNA sequences synthesized from bovine lens messenger RNAs was constructed. Clones coding for five different beta-crystallin subunits: beta B1, beta B3, beta Bp, beta s, beta A3 (and beta A1), were identified by means of hybridization selection, followed by one- and two-dimensional gel electrophoresis of the translational products. Under rather stringent conditions each of these clones hybridizes with its corresponding mRNA and does not show significant cross-hybridization with mRNAs coding for other beta-crystallins, except in the case of the homologous beta A3 and beta A1-crystallins. The beta A3 and beta A1 subunits seem to be encoded by one mRNA using two different AUG codons as start position for translation. We have also determined the nucleotide sequence of a beta B1-crystallin cDNA (pBL beta B1) which enabled us to deduce the complete amino acid sequence of the protein. The beta B1-crystallin, a characteristic component of the high molecular weight crystallin aggregate (beta H), is internally homologous both at DNA and protein level as has been reported for gamma- and other beta-crystallins. This is in agreement with the idea that these proteins had a common ancestral precursor gene that internally duplicated. The G + C content of the coding sequence of beta B1 is very high: 67% overall and even 84.2% for the first 170 nucleotides, due to a remarkable non-random codon usage. A proline/alanine repetition in the N-terminal domain of the protein is encoded by a repetitive "simple" DNA sequence.
J Mol Biol 1984 Dec 15
PMID:Bovine beta-crystallin complementary DNA clones. Alternating proline/alanine sequence of beta B1 subunit originates from a repetitive DNA sequence. 652 79

We report the X-ray structure analysis and refinement at 1.9 A resolution of calf gamma-II crystallin, a lens-specific protein. The sequence of Croft (1972) has been modified to give a polypeptide chain of 174 residues (cf. 165). The protein has a symmetrical, hierarchical structure of two globular domains each comprising two similar "Greek key" motifs, consecutive along the polypeptide chain, and related by a pseudo 2-fold axis. The two domains pack together with a single connection and are related by a further pseudo 2-fold axis which bisects the angle between the intra-domain dyads. Forty-two pairs of C alpha positions for the two most similar motifs have root-mean-square separation at best fit of 0.69 A. The N and C-terminal domains gave root-mean-square separation of 0.89 A for 82 pairs of C alpha atoms at best fit. In each domain the two Greek key motifs form a pair of four-stranded antiparallel beta-pleated sheets, each sheet composed of three stands from one motif and one from the other. The sheets pack together in a wedge shape, closed at the top by the loops connecting the third and fourth strands of each motif. The first two strands of each motif form an extended beta-hairpin which is folded on to the beta-sheet. The packing of each motif into the globular domains involves a staggered bilayer of side-chains between each pair of beta-sheets which does not preserve the pseudo 2-fold axes observed in the C alpha position topology. In the core of each domain there are interactions between polarizable aromatic groups and sulphur-containing residues which may contribute to stability and may also serve to protect aromatic side-chains from ultraviolet light damage in the lens. At the surface of the molecule over half the ionic side-chains are closely paired, which probably stabilizes the tertiary fold and may reduce the water bound. Crystal lattice interactions are described which may be similar to those occurring in vivo in the lens between crystallins. Seven cysteine residues have been identified in the structure and these may have a role in the thermodynamic stability of the molecule, its intermolecular interactions under the normal reducing conditions of the lens, and also in the aggregation and cross-linking which occur in some forms of cataract. Three of these residues, Cys18, Cys23 and Cys74, form a cluster in the N-terminal domain.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1983 Oct 15
PMID:X-ray analysis of the eye lens protein gamma-II crystallin at 1.9 A resolution. 663 60

Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase expressed at very high levels in the lenses of two groups of mammals: camelids and some hystricomorph rodents. It is also expressed at very low levels in all other species tested. Comparative analysis of the mechanisms mediating the high expression of this enzyme/crystallin in the lens of the Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided evidence for independent recruitment of this enzyme as a lens crystallin in both species and allowed us to elucidate for the first time the mechanism of lens recruitment of an enzyme-crystallin. The data presented here show that in both species such recruitment most likely occurred through the generation of new lens promoters from nonfunctional intron sequences by the accumulation of point mutations and/or small deletions and insertions. These results further support the idea that recruitment of CRYZ resulted from an adaptive process in which the high expression of CRYZ in the lens provides some selective advantage rather than from a purely neutral evolutionary process.
Mol Biol Evol 1995 Sep
PMID:Evidence for independent recruitment of zeta-crystallin/quinone reductase (CRYZ) as a crystallin in camelids and hystricomorph rodents. 747 24

Analysis of nascent gamma B-crystallin peptides accumulating during in vitro translation in a rabbit reticulocyte lysate cell-free system was carried out. As a consequence of the irregular distribution of rare codons along the polypeptide chain of gamma B-crystallin, translation of the two-domain protein is a non-uniform process characterized by specific pauses. One of the major delays occurs during the translation of the connecting peptide between the domains. Comparing the kinetics of translation of natural gamma B-crystallin and its circularly permutated variant (with the order of the N- and C-terminal domains exchanged) reveals that the natural N-terminal domain is translated faster than the C-terminal one. Since the N-terminal domain in natural gamma B-crystallin is known to be more stable and to fold faster than the C-terminal one [E.-M. Mayr et al. (1994) J. Mol. Biol. 235, 84-88], the present data suggest that the translation rates are optimized to tune the synthesis and folding of the nascent polypeptide chain. In this connection, the pause in the linker region between the domains provides a delay allowing the correct folding of the N-terminal domain and its subsequent assistance in the stabilization of the C-terminal one.
 ...
PMID:Kinetics of translation of gamma B crystallin and its circularly permutated variant in an in vitro cell-free system: possible relations to codon distribution and protein folding. 749 40


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