4m5s

Human alphaB crystallin core domain in complex with C-terminal peptide

spinqualitylabelsall models 4m5s, resolution 1.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4m5s is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SIN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CRYAB_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. Function CRYAB_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 PubMed Mammalian small heat-shock proteins (sHSPs) are molecular chaperones that form polydisperse and dynamic complexes with target proteins, serving as a first line of defense in preventing their aggregation into either amorphous deposits or amyloid fibrils. Their apparently broad target specificity makes sHSPs attractive for investigating ways to tackle disorders of protein aggregation. The two most abundant sHSPs in human tissue are alphaB-crystallin (ABC) and HSP27; here we present high-resolution structures of their core domains (cABC, cHSP27), each in complex with a segment of their respective C-terminal regions. We find that both truncated proteins dimerize, and although this interface is labile in the case of cABC, in cHSP27 the dimer can be cross-linked by an intermonomer disulfide linkage. Using cHSP27 as a template, we have designed an equivalently locked cABC to enable us to investigate the functional role played by oligomerization, disordered N and C termini, subunit exchange, and variable dimer interfaces in ABC. We have assayed the ability of the different forms of ABC to prevent protein aggregation in vitro. Remarkably, we find that cABC has chaperone activity comparable to that of the full-length protein, even when monomer dissociation is restricted through disulfide linkage. Furthermore, cABC is a potent inhibitor of amyloid fibril formation and, by slowing the rate of its aggregation, effectively reduces the toxicity of amyloid-beta peptide to cells. Overall we present a small chaperone unit together with its atomic coordinates that potentially enables the rational design of more effective chaperones and amyloid inhibitors. The structured core domain of alphaB-crystallin can prevent amyloid fibrillation and associated toxicity.,Hochberg GK, Ecroyd H, Liu C, Cox D, Cascio D, Sawaya MR, Collier MP, Stroud J, Carver JA, Baldwin AJ, Robinson CV, Eisenberg DS, Benesch JL, Laganowsky A Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):E1562-70. doi:, 10.1073/pnas.1322673111. Epub 2014 Apr 7. PMID:24711386 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Crystallin 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA