Review

. 2017 Jul;22(4):601-611.

doi: 10.1007/s12192-017-0787-8. Epub 2017 Mar 31.

The growing world of small heat shock proteins: from structure to functions

Serena Carra¹, Simon Alberti², Patrick A Arrigo^{3

4}, Justin L Benesch⁵, Ivor J Benjamin⁶, Wilbert Boelens⁷, Britta Bartelt-Kirbach⁸, Bianca J J M Brundel^{9

10}, Johannes Buchner¹¹, Bernd Bukau^{12

13}, John A Carver¹⁴, Heath Ecroyd¹⁵, Cecilia Emanuelsson¹⁶, Stephanie Finet¹⁷, Nikola Golenhofen⁸, Pierre Goloubinoff¹⁸, Nikolai Gusev¹⁹, Martin Haslbeck¹¹, Lawrence E Hightower²⁰, Harm H Kampinga²¹, Rachel E Klevit²², Krzysztof Liberek²³, Hassane S Mchaourab²⁴, Kathryn A McMenimen²⁵, Angelo Poletti²⁶, Roy Quinlan²⁷, Sergei V Strelkov²⁸, Melinda E Toth²⁹, Elizabeth Vierling^{30

31}, Robert M Tanguay³²

Affiliations

¹ Department of Biomedical, Metabolic and Neural Sciences, and Centre for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy.
² Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
³ Université de Lyon, 69622, Lyon, France.
⁴ CNRS, UMR 5310, INSERM U1217, Institut NeuroMyoGène, Université Lyon 1, 69100, Villeurbanne, France.
⁵ Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK.
⁶ Department of Biochemistry, University of Utah, Salt Lake City, UT, 84112-5650, USA.
⁷ Biomolecular Chemistry, 284, Radboud University, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁸ Institute of Anatomy and Cell Biology, University of Ulm, 89081, Ulm, Germany.
⁹ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁰ Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
¹¹ Technische Universitat Munchen, Munich, Germany.
¹² Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
¹³ German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
¹⁴ The Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia.
¹⁵ Illawara Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
¹⁶ Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, 221 00, Lund, Sweden.
¹⁷ IMPMC UMR7590, CNRS, UPMC Paris 6, 4 place Jussieu, Paris, France.
¹⁸ Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
¹⁹ Department of Biochemistry, School of Biology, Moscow State University, Moscow, 119991, Russia.
²⁰ Department of Molecular & Cell Biology, University of Connecticut, 91 North Eagleville Road, Storrs, CT, 06269-3125, USA.
²¹ Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands.
²² Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
²³ Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and the Medical University of Gdańsk, Gdańsk, Poland.
²⁴ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
²⁵ Departments of Pathology, Biological Chemistry, and Medicinal Chemistry and the Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
²⁶ Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Milan, Italy.
²⁷ Department of Biosciences and the Biophysical Sciences Institute, University of Durham, Durham, UK.
²⁸ Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
²⁹ Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
³⁰ Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, 01003, USA.
³¹ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
³² Laboratory of Cell & Developmental Genetics, IBIS, and Department of Molecular Biology, Medical Biochemistry and Pathology, Medical School, Université Laval, Québec (Qc), G1V 0A6, Canada. Robert.tanguay@fmed.ulaval.ca.

PMID: 28364346
PMCID: PMC5465036
DOI: 10.1007/s12192-017-0787-8

Review

The growing world of small heat shock proteins: from structure to functions

Serena Carra et al. Cell Stress Chaperones. 2017 Jul.

. 2017 Jul;22(4):601-611.

doi: 10.1007/s12192-017-0787-8. Epub 2017 Mar 31.

Authors

Affiliations

¹ Department of Biomedical, Metabolic and Neural Sciences, and Centre for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy.
² Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
³ Université de Lyon, 69622, Lyon, France.
⁴ CNRS, UMR 5310, INSERM U1217, Institut NeuroMyoGène, Université Lyon 1, 69100, Villeurbanne, France.
⁵ Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK.
⁶ Department of Biochemistry, University of Utah, Salt Lake City, UT, 84112-5650, USA.
⁷ Biomolecular Chemistry, 284, Radboud University, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁸ Institute of Anatomy and Cell Biology, University of Ulm, 89081, Ulm, Germany.
⁹ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁰ Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
¹¹ Technische Universitat Munchen, Munich, Germany.
¹² Center for Molecular Biology of the University of Heidelberg (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
¹³ German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
¹⁴ The Research School of Chemistry, The Australian National University, Acton, ACT, 2601, Australia.
¹⁵ Illawara Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW, 2522, Australia.
¹⁶ Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, 221 00, Lund, Sweden.
¹⁷ IMPMC UMR7590, CNRS, UPMC Paris 6, 4 place Jussieu, Paris, France.
¹⁸ Department of Plant Molecular Biology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
¹⁹ Department of Biochemistry, School of Biology, Moscow State University, Moscow, 119991, Russia.
²⁰ Department of Molecular & Cell Biology, University of Connecticut, 91 North Eagleville Road, Storrs, CT, 06269-3125, USA.
²¹ Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands.
²² Department of Biochemistry, University of Washington, Seattle, WA, 98195, USA.
²³ Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and the Medical University of Gdańsk, Gdańsk, Poland.
²⁴ Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232, USA.
²⁵ Departments of Pathology, Biological Chemistry, and Medicinal Chemistry and the Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
²⁶ Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Centro di Eccellenza sulle Malattie Neurodegenerative, Università degli Studi di Milano, Milan, Italy.
²⁷ Department of Biosciences and the Biophysical Sciences Institute, University of Durham, Durham, UK.
²⁸ Laboratory for Biocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
²⁹ Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Szeged, Hungary.
³⁰ Biochemistry and Molecular Biology, University of Massachusetts, Amherst, MA, 01003, USA.
³¹ Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.
³² Laboratory of Cell & Developmental Genetics, IBIS, and Department of Molecular Biology, Medical Biochemistry and Pathology, Medical School, Université Laval, Québec (Qc), G1V 0A6, Canada. Robert.tanguay@fmed.ulaval.ca.

PMID: 28364346
PMCID: PMC5465036
DOI: 10.1007/s12192-017-0787-8

Abstract

Small heat shock proteins (sHSPs) are present in all kingdoms of life and play fundamental roles in cell biology. sHSPs are key components of the cellular protein quality control system, acting as the first line of defense against conditions that affect protein homeostasis and proteome stability, from bacteria to plants to humans. sHSPs have the ability to bind to a large subset of substrates and to maintain them in a state competent for refolding or clearance with the assistance of the HSP70 machinery. sHSPs participate in a number of biological processes, from the cell cycle, to cell differentiation, from adaptation to stressful conditions, to apoptosis, and, even, to the transformation of a cell into a malignant state. As a consequence, sHSP malfunction has been implicated in abnormal placental development and preterm deliveries, in the prognosis of several types of cancer, and in the development of neurological diseases. Moreover, mutations in the genes encoding several mammalian sHSPs result in neurological, muscular, or cardiac age-related diseases in humans. Loss of protein homeostasis due to protein aggregation is typical of many age-related neurodegenerative and neuromuscular diseases. In light of the role of sHSPs in the clearance of un/misfolded aggregation-prone substrates, pharmacological modulation of sHSP expression or function and rescue of defective sHSPs represent possible routes to alleviate or cure protein conformation diseases. Here, we report the latest news and views on sHSPs discussed by many of the world's experts in the sHSP field during a dedicated workshop organized in Italy (Bertinoro, CEUB, October 12-15, 2016).

Keywords: Hsp27; Neurological diseases; Protein aggregates; Protein conformation; Protein homeostasis; Small heat shock proteins.

PubMed Disclaimer

Cited by

Combined Proteome and Transcriptome Analysis of Heat-Primed Azalea Reveals New Insights Into Plant Heat Acclimation Memory.
Wang X, Li Z, Liu B, Zhou H, Elmongy MS, Xia Y. Wang X, et al. Front Plant Sci. 2020 Aug 19;11:1278. doi: 10.3389/fpls.2020.01278. eCollection 2020. Front Plant Sci. 2020. PMID: 32973837 Free PMC article.
Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson's Disease?
Navarro-Zaragoza J, Cuenca-Bermejo L, Almela P, Laorden ML, Herrero MT. Navarro-Zaragoza J, et al. Int J Mol Sci. 2021 Mar 16;22(6):3038. doi: 10.3390/ijms22063038. Int J Mol Sci. 2021. PMID: 33809767 Free PMC article. Review.
Small HSPs at the crossroad between protein aggregation, autophagy and unconventional secretion: clinical implications and potential therapeutic opportunities in the context of neurodegenerative diseases.
Bonavita R, Vitale F, Verdicchio LV, Williams SV, Caporaso MG, Fleming A, Renna M. Bonavita R, et al. Front Cell Dev Biol. 2025 May 2;13:1538377. doi: 10.3389/fcell.2025.1538377. eCollection 2025. Front Cell Dev Biol. 2025. PMID: 40385290 Free PMC article. Review.
Probing the Dissociation of Protein Complexes by Means of Gas-Phase H/D Exchange Mass Spectrometry.
Mistarz UH, Chandler SA, Brown JM, Benesch JLP, Rand KD. Mistarz UH, et al. J Am Soc Mass Spectrom. 2019 Jan;30(1):45-57. doi: 10.1007/s13361-018-2064-1. Epub 2018 Nov 20. J Am Soc Mass Spectrom. 2019. PMID: 30460642
The Small Heat Shock Protein, HSPB1, Interacts with and Modulates the Physical Structure of Membranes.
Csoboz B, Gombos I, Kóta Z, Dukic B, Klement É, Varga-Zsíros V, Lipinszki Z, Páli T, Vígh L, Török Z. Csoboz B, et al. Int J Mol Sci. 2022 Jun 30;23(13):7317. doi: 10.3390/ijms23137317. Int J Mol Sci. 2022. PMID: 35806322 Free PMC article.

See all "Cited by" articles

References

1. Ahrman E, Gustavsson N, Hultschig C, Boelens WC, Emanuelsson CS. Small heat shock proteins prevent aggregation of citrate synthase and bind to the N-terminal region which is absent in thermostable forms of citrate synthase. Extremophiles. 2007;11:659–666. doi: 10.1007/s00792-007-0080-3. - DOI - PubMed
1. Ahrman E, Lambert W, Aquilina JA, Robinson CV, Emanuelsson CS. Chemical cross-linking of the chloroplast localized small heat-shock protein, Hsp21, and the model substrate citrate synthase. Protein Sci. 2007;16:1464–1478. doi: 10.1110/ps.072831607. - DOI - PMC - PubMed
1. Aquilina JA, Benesch JL, Ding LL, Yaron O, Horwitz J, Robinson CV. Phosphorylation of alphaB-crystallin alters chaperone function through loss of dimeric substructure. J Biol Chem. 2004;279:28675–28680. doi: 10.1074/jbc.M403348200. - DOI - PubMed
1. Arrigo AP. sHsp as novel regulators of programmed cell death and tumorigenicity. Pathologie-biologie. 2000;48:280–288. - PubMed
1. Arrigo AP. The cellular “networking” of mammalian Hsp27 and its functions in the control of protein folding, redox state and apoptosis. Adv Exp Med Biol. 2007;594:14–26. doi: 10.1007/978-0-387-39975-1_2. - DOI - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

The growing world of small heat shock proteins: from structure to functions

Affiliations

The growing world of small heat shock proteins: from structure to functions

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials

Miscellaneous