A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis
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 tran...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/07304 |
| _version_ | 1828166162546950144 |
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| author | Ponni Rajagopal Eric Tse Andrew J Borst Scott P Delbecq Lei Shi Daniel R Southworth Rachel E Klevit |
| author_facet | Ponni Rajagopal Eric Tse Andrew J Borst Scott P Delbecq Lei Shi Daniel R Southworth Rachel E Klevit |
| author_sort | Ponni Rajagopal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:57:14Z |
| format | Article |
| id | doaj.art-90e3f855f2834c77b652e9c69fe0234b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:57:14Z |
| publishDate | 2015-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-90e3f855f2834c77b652e9c69fe0234b2022-12-22T03:52:46ZengeLife Sciences Publications LtdeLife2050-084X2015-05-01410.7554/eLife.07304A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosisPonni Rajagopal0Eric Tse1Andrew J Borst2Scott P Delbecq3Lei Shi4Daniel R Southworth5Rachel E Klevit6Department of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesSmall 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.https://elifesciences.org/articles/07304protein chaperoneheat shock proteinprotein aggregationelectron microscopyNMR |
| spellingShingle | Ponni Rajagopal Eric Tse Andrew J Borst Scott P Delbecq Lei Shi Daniel R Southworth Rachel E Klevit A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis eLife protein chaperone heat shock protein protein aggregation electron microscopy NMR |
| title | A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis |
| title_full | A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis |
| title_fullStr | A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis |
| title_full_unstemmed | A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis |
| title_short | A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis |
| title_sort | conserved histidine modulates hspb5 structure to trigger chaperone activity in response to stress related acidosis |
| topic | protein chaperone heat shock protein protein aggregation electron microscopy NMR |
| url | https://elifesciences.org/articles/07304 |
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