3j07
From Proteopedia
Model of a 24mer alphaB-crystallin multimer
Structural highlights
DiseaseCRYAB_HUMAN Posterior polar cataract;Alpha-crystallinopathy;Zonular cataract;Familial isolated dilated cardiomyopathy;Fatal infantile hypertonic myofibrillar myopathy. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionCRYAB_HUMAN May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. Publication Abstract from PubMedThe small heat shock protein (sHSP) alphaB-crystallin (alphaB) plays a key role in the cellular protection system against stress. For decades, high-resolution structural studies on heterogeneous sHSPs have been confounded by the polydisperse nature of alphaB oligomers. We present an atomic-level model of full-length alphaB as a symmetric 24-subunit multimer based on solid-state NMR, small-angle X-ray scattering (SAXS), and EM data. The model builds on our recently reported structure of the homodimeric alpha-crystallin domain (ACD) and C-terminal IXI motif in the context of the multimer. A hierarchy of interactions contributes to build multimers of varying sizes: Interactions between two ACDs define a dimer, three dimers connected by their C-terminal regions define a hexameric unit, and variable interactions involving the N-terminal region define higher-order multimers. Within a multimer, N-terminal regions exist in multiple environments, contributing to the heterogeneity observed by NMR. Analysis of SAXS data allows determination of a heterogeneity parameter for this type of system. A mechanism of multimerization into higher-order asymmetric oligomers via the addition of up to six dimeric units to a 24-mer is proposed. The proposed asymmetric multimers explain the homogeneous appearance of alphaB in negative-stain EM images and the known dynamic exchange of alphaB subunits. The model of alphaB provides a structural basis for understanding known disease-associated missense mutations and makes predictions concerning substrate binding and the reported fibrilogenesis of alphaB. N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity.,Jehle S, Vollmar BS, Bardiaux B, Dove KK, Rajagopal P, Gonen T, Oschkinat H, Klevit RE Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6409-14. doi:, 10.1073/pnas.1014656108. Epub 2011 Apr 4. PMID:21464278[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Bardiaux B | Dove KK | Gonen T | Jehle S | Klevit RE | Oschkinat H | Rajagopal P | Vollmar B
