2N0K

Chemical shift assignments and structure of the alpha-crystallin domain from human, HSPB5

Summary for 2N0K

• Entry DOI: 10.2210/pdb2n0k/pdb
• NMR Information: BMRB: 25527
• Descriptor: Alpha-crystallin B chain (1 entity in total)
• Functional Keywords: crystallin, human, acd, protein, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P02511
• Total number of polymer chains: 2
• Total formula weight: 20400.99

Authors

Rajagopal, P.,Klevit, R.E.,Shi, L.,Baker, D. (deposition date: 2015-03-09, release date: 2015-06-03, Last modification date: 2024-05-15)

Primary citation

Rajagopal, P.,Tse, E.,Borst, A.J.,Delbecq, S.P.,Shi, L.,Southworth, D.R.,Klevit, R.E.
A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis.
Elife, 4:-, 2015

PubMed Abstract: Small 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.

PubMed: 25962097
DOI: 10.7554/eLife.07304

Experimental method

SOLUTION NMR