title: A first line of stress defense: small heat shock proteins and their function in protein homeostasis.
abstract: Small heat shock proteins (sHsps) are virtually ubiquitous molecular chaperones that can prevent the irreversible aggregation of denaturing proteins. sHsps complex with a variety of non-native proteins in an ATP-independent manner and, in the context of the stress response, form a first line of defense against protein aggregation in order to maintain protein homeostasis. In vertebrates, they act to maintain the clarity of the eye lens, and in humans, sHsp mutations are linked to myopathies and neuropathies. Although found in all domains of life, sHsps are quite diverse and have evolved independently in metazoans, plants and fungi. sHsp monomers range in size from approximately 12 to 42kDa and are defined by a conserved β-sandwich α-crystallin domain, flanked by variable N- and C-terminal sequences. Most sHsps form large oligomeric ensembles with a broad distribution of different, sphere- or barrel-like oligomers, with the size and structure of the oligomers dictated by features of the N- and C-termini. The activity of sHsps is regulated by mechanisms that change the equilibrium distribution in tertiary features and/or quaternary structure of the sHsp ensembles. Cooperation and/or co-assembly between different sHsps in the same cellular compartment add an underexplored level of complexity to sHsp structure and function.
authors: Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85 748 Garching, Germany. Electronic address: martin.haslbeck@tum.de.
authors: Martin
authors: M
authors: Haslbeck
authors: Department of Biochemistry and Molecular Biology, University of Massachusetts, Life Science Laboratories, N329 240 Thatcher Road, Amherst, MA 01003-9364, USA. Electronic address: vierling@biochem.umass.edu.
authors: Elizabeth
authors: E
authors: Vierling
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D050888:Heat-Shock Proteins, Small / Q000737:chemistry / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000502:physiology; D020836:Protein Structure, Quaternary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D050888:Heat-Shock Proteins, Small; D018832:Molecular Chaperones; D011506:Proteins
keywords: molecular chaperones; protein aggregation; protein folding; stress response; α-crystallin