Biomaterial Database

Alpha-crystallin as a molecular chaperone. 1999

B K Derham, and J J Harding

Nuffield Laboratory of Ophthalmology, University of Oxford, UK.

The role of alpha-crystallin as a molecular chaperone may explain how the lens stays transparent for so long. Alpha-crystallin prevents the aggregation of other lens crystallins and proteins that have become unfolded by "trapping" the protein in a high molecular weight complex. It also protects enzyme activities. The substrate protein may interact while in a molten globule state. Alpha-crystallin predominantly binds to proteins very early in the denaturation pathways. The amphiphilic nature of alpha-crystallin, a polar C-terminal-region and a hydrophobic N-terminal-region are all essential for chaperone function. The flexible C-terminal extension maintains solubility and can bind to opposing charged residues of unfolding proteins. Hydrophobic regions in the N-terminal region then hold the unfolded protein. Specific areas important for chaperone binding and function have been identified throughout the N-terminal-region, connecting peptide and C-terminal extension. After a substantial amount of chemical data and models, cryo-EM images of alpha-crystallin have confirmed a variable 3D surface with a hollow interior. Alpha-crystallin taken from the lens nucleus shows an age-dependent decrease in chaperone function. High molecular weight aggregates and alpha-crystallin found within the nucleus from clear and cataract lenses have reduced chaperone function. Post-translational modifications, known to occur during ageing, such as glycation, carbamylation, oxidation, phosphorylation and truncation cause a decrease in chaperone function. Alpha-crystallin is expressed outside the lens. AlphaB-crystallin can be induced by heat shock in many tissues where it is translocated from cytoplasm to nucleus. Increased expression of alphaB-crystallin has been seen in many pathological states. Conformational disorders, including cataract may have a common aetiology and potentially a common therapy.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003459	Crystallins	A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses.	Lens Proteins,Crystallin,Eye Lens Protein,Lens Protein, Eye,Protein, Eye Lens,Proteins, Lens
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016415	Sequence Alignment	The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.	Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D017386	Sequence Homology, Amino Acid	The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.	Homologous Sequences, Amino Acid,Amino Acid Sequence Homology,Homologs, Amino Acid Sequence,Homologs, Protein Sequence,Homology, Protein Sequence,Protein Sequence Homologs,Protein Sequence Homology,Sequence Homology, Protein,Homolog, Protein Sequence,Homologies, Protein Sequence,Protein Sequence Homolog,Protein Sequence Homologies,Sequence Homolog, Protein,Sequence Homologies, Protein,Sequence Homologs, Protein