1ytq
From Proteopedia
Structure of Native Human Beta B2 Crystallin
Structural highlights
Disease[CRBB2_HUMAN] Cerulean cataract;Nuclear cataract;Cataract, Coppock-like;Cataract-microcornea syndrome;Total congenital cataract;Cataract with Y-shaped suture opacities. Cataract, congenital, cerulean type, 2 (CCA2) [MIM:601547]: A cerulean form of autosomal dominant congenital cataract. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] Cataract, sutural, with punctate and cerulean opacities (CSPC) [MIM:607133]: A form of cataract characterized by white opacification around the anterior and posterior Y sutures, and grayish and bluish, spindle shaped, oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots are more concentrated towards the peripheral layers and do not delineate the embryonal or fetal nucleus. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots is observed among affected subjects. Note=The disease is caused by mutations affecting the gene represented in this entry. Cataract Coppock-like (CCL) [MIM:604307]: A congenital pulverulent disk-like opacity involving the embryonic nucleus with many tiny white dots in the lamellar portion of the lens. It is usually bilateral and dominantly inherited. Note=The disease is caused by mutations affecting the gene represented in this entry.[2] Function[CRBB2_HUMAN] Crystallins are the dominant structural components of the vertebrate eye lens. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe superfamily of eye lens betagamma-crystallins is highly modularized, with Greek key motifs being used to form symmetric domains. Sequences of monomeric gamma-crystallins and oligomeric beta-crystallins fold into two domains that pair about a further conserved symmetric interface. Conservation of this assembly interface by domain swapping is the device adopted by family member betaB2-crystallin to form a solution dimer. However, the betaB1-crystallin solution dimer is formed from an interface used by the domain-swapped dimer to form a tetramer in the crystal lattice. Comparison of these two structures indicated an intriguing relationship between linker conformation, interface ion pair networks, and higher assembly. Here the X-ray structure of recombinant human betaB2-crystallin showed that domain swapping was determined by the sequence and not assembly conditions. The solution characteristics of mutants that were designed to alter an ion pair network at a higher assembly interface and a mutant that changed a proline showed they remained dimeric. X-ray crystallography showed that the dimeric mutants did not reverse domain swapping. Thus, the sequence of betaB2-crystallin appears well optimized for domain swapping. However, a charge-reversal mutation to the conserved domain-pairing interface showed drastic changes to solution behavior. It appears that the higher assembly of the betagamma-crystallin domains has exploited symmetry to create diversity while avoiding aggregation. These are desirable attributes for proteins that have to exist at very high concentration for a very long time. Mutation of interfaces in domain-swapped human betaB2-crystallin.,Smith MA, Bateman OA, Jaenicke R, Slingsby C Protein Sci. 2007 Apr;16(4):615-25. Epub 2007 Feb 27. PMID:17327390[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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