2n0k
From Proteopedia
Chemical shift assignments and structure of the alpha-crystallin domain from human, HSPB5
Structural highlights
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 PubMedSmall heat shock proteins (sHSPs) are essential 'holdase' chaperones that form large assemblies and respond dynamically to pH and temperature stresses to protect client proteins from aggregation. While the alpha-crystallin domain (ACD) dimer of sHSPs is the universal building block, how the ACD transmits structural changes in response to stress to promote holdase activity is unknown. We found that the dimer interface of HSPB5 is destabilized over physiological pHs and a conserved histidine (His-104) controls interface stability and oligomer structure in response to acidosis. Destabilization by pH or His-104 mutation shifts the ACD from dimer to monomer but also results in a large expansion of HSPB5 oligomer states. Remarkably, His-104 mutant-destabilized oligomers are efficient holdases that reorganize into structurally distinct client-bound complexes. Our data support a model for sHSP function wherein cell stress triggers small perturbations that alter the ACD building blocks to unleash a cryptic mode of chaperone action. A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis.,Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Southworth DP, Klevit RE Elife. 2015 May 11;4. doi: 10.7554/eLife.07304. PMID:25962097[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Baker, D | Klevit, R E | Rajagopal, P | Shi, L | Acd | Crystallin | Metal binding protein | Protein
