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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 DR, Klevit RE
Elife 4 (2015)
Related entries: 2klr, 3j07

Cited: 35 times
EuropePMC logo PMID: 25962097

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.

Reviews - 2n0k mentioned but not cited (2)

  1. Mechanisms of Small Heat Shock Proteins. Janowska MK, Baughman HER, Woods CN, Klevit RE. Cold Spring Harb Perspect Biol 11 a034025 (2019)
  2. The multifaceted nature of αB-crystallin. Hayashi J, Carver JA. Cell Stress Chaperones 25 639-654 (2020)

Articles - 2n0k mentioned but not cited (2)

  1. 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 DR, Klevit RE. Elife 4 (2015)
  2. Interplay of disordered and ordered regions of a human small heat shock protein yields an ensemble of 'quasi-ordered' states. Clouser AF, Baughman HE, Basanta B, Guttman M, Nath A, Klevit RE. Elife 8 e50259 (2019)


Reviews citing this publication (8)

  1. Protein-Protein Interactions in the Molecular Chaperone Network. Freilich R, Arhar T, Abrams JL, Gestwicki JE. Acc Chem Res 51 940-949 (2018)
  2. Progression of the role of CRYAB in signaling pathways and cancers. Zhang J, Liu J, Wu J, Li W, Chen Z, Yang L. Onco Targets Ther 12 4129-4139 (2019)
  3. Protein plasticity underlines activation and function of ATP-independent chaperones. Suss O, Reichmann D. Front Mol Biosci 2 43 (2015)
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  5. Protein folding by NMR. Zhuravleva A, Korzhnev DM. Prog Nucl Magn Reson Spectrosc 100 52-77 (2017)
  6. α-Crystallins in the Vertebrate Eye Lens: Complex Oligomers and Molecular Chaperones. Sprague-Piercy MA, Rocha MA, Kwok AO, Martin RW. Annu Rev Phys Chem 72 143-163 (2021)
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  8. Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers. Ksila M, Ghzaiel I, Sassi K, Zarrouk A, Leoni V, Poli G, Rezig L, Pires V, Meziane S, Atanasov AG, Hammami S, Hammami M, Masmoudi-Kouki O, Hamdi O, Jouanny P, Samadi M, Vejux A, Ghrairi T, Lizard G. Adv Exp Med Biol 1440 379-400 (2024)

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  2. HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation. Baughman HER, Clouser AF, Klevit RE, Nath A. J Biol Chem 293 2687-2700 (2018)
  3. A Mechanism of Subunit Recruitment in Human Small Heat Shock Protein Oligomers. Delbecq SP, Rosenbaum JC, Klevit RE. Biochemistry 54 4276-4284 (2015)
  4. A prion-like domain in Hsp42 drives chaperone-facilitated aggregation of misfolded proteins. Grousl T, Ungelenk S, Miller S, Ho CT, Khokhrina M, Mayer MP, Bukau B, Mogk A. J Cell Biol 217 1269-1285 (2018)
  5. The functional roles of the unstructured N- and C-terminal regions in αB-crystallin and other mammalian small heat-shock proteins. Carver JA, Grosas AB, Ecroyd H, Quinlan RA. Cell Stress Chaperones 22 627-638 (2017)
  6. Release of a disordered domain enhances HspB1 chaperone activity toward tau. Baughman HER, Pham TT, Adams CS, Nath A, Klevit RE. Proc Natl Acad Sci U S A 117 2923-2929 (2020)
  7. Mechanistic insights into the switch of αB-crystallin chaperone activity and self-multimerization. Liu Z, Wang C, Li Y, Zhao C, Li T, Li D, Zhang S, Liu C. J Biol Chem 293 14880-14890 (2018)
  8. pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1. Clouser AF, Klevit RE. Cell Stress Chaperones 22 569-575 (2017)
  9. Mechanism of Action of VP1-001 in cryAB(R120G)-Associated and Age-Related Cataracts. Molnar KS, Dunyak BM, Su B, Izrayelit Y, McGlasson-Naumann B, Hamilton PD, Qian M, Covey DF, Gestwicki JE, Makley LN, Andley UP. Invest Ophthalmol Vis Sci 60 3320-3331 (2019)
  10. Regulation of chaperone function by coupled folding and oligomerization. Mas G, Burmann BM, Sharpe T, Claudi B, Bumann D, Hiller S. Sci Adv 6 eabc5822 (2020)
  11. Conditional Disorder in Small Heat-shock Proteins. Alderson TR, Ying J, Bax A, Benesch JLP, Baldwin AJ. J Mol Biol 432 3033-3049 (2020)
  12. CRYAB predicts clinical prognosis and is associated with immunocyte infiltration in colorectal cancer. Deng J, Chen X, Zhan T, Chen M, Yan X, Huang X. PeerJ 9 e12578 (2021)
  13. HSPB5 engages multiple states of a destabilized client to enhance chaperone activity in a stress-dependent manner. Delbecq SP, Klevit RE. J Biol Chem 294 3261-3270 (2019)
  14. Chaperone activity of human small heat shock protein-GST fusion proteins. Arbach H, Butler C, McMenimen KA. Cell Stress Chaperones 22 503-515 (2017)
  15. αA-crystallin-derived minichaperone stabilizes αAG98R-crystallin by affecting its zeta potential. Phadte AS, Santhoshkumar P, Sharma KK. Mol Vis 24 297-304 (2018)
  16. Role of methylation-related genes CRYAB and SLC39A11 in the occurrence and development of lung adenocarcinoma. Wang S, Gui P, Liu Y, Liang X, Fan B, Shang W, Wang D, Shao S, Sun L. Ann Transl Med 10 1126 (2022)
  17. The engineered expression of secreted HSPB5-Fc in CHO cells exhibits cytoprotection in vitro. Li J, Yu J, Xue W, Huang H, Yan L, Sang F, An S, Zhang J, Wang M, Zhang J, Li H, Cui X, He J, Hu Y. BMC Biotechnol 21 39 (2021)
  18. HspB5 Chaperone Structure and Activity Are Modulated by Chemical-Scale Interactions in the ACD Dimer Interface. Wang C, Teng L, Liu ZS, Kamalova A, McMenimen KA. Int J Mol Sci 25 471 (2023)
  19. Network Pharmacology-Based Strategy to Reveal the Mechanism of Cassiae Semen against Cataracts. Zhong Y, Chen RF, Fang YF. Comput Math Methods Med 2022 5654120 (2022)
  20. Sample pH Can Drift during Native Mass Spectrometry Experiments: Results from Ratiometric Fluorescence Imaging. Gadzuk-Shea MM, Hubbard EE, Gozzo TA, Bush MF. J Am Soc Mass Spectrom 34 1675-1684 (2023)
  21. The permanently chaperone-active small heat shock protein Hsp17 from Caenorhabditis elegans exhibits topological separation of its N-terminal regions. Strauch A, Rossa B, Köhler F, Haeussler S, Mühlhofer M, Rührnößl F, Körösy C, Bushman Y, Conradt B, Haslbeck M, Weinkauf S, Buchner J. J Biol Chem 299 102753 (2023)
  22. The role of CRYAB in tumor prognosis and immune infiltration: A Pan-cancer analysis. Cheng L, Zou X, Wang J, Zhang J, Mo Z, Huang H. Front Surg 9 1117307 (2022)
  23. Twin-arginine translocase component TatB performs folding quality control via a chaperone-like activity. Taw MN, Boock JT, Sotomayor B, Kim D, Rocco MA, Waraho-Zhmayev D, DeLisa MP. Sci Rep 12 14862 (2022)


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