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    The Family of Small Heat Shock Proteins: Assembly and Binding Functions

    Slingsby, Christine and Clark, A.R. (2016) The Family of Small Heat Shock Proteins: Assembly and Binding Functions. In: Gierasch, L.M. and Horwich, A.L. and Slingsby, Christine and Wickner, S. and Agard, D. (eds.) Structure and Action of Molecular Chaperones: Machines that Assist Protein Folding in the Cell. Series in Structural Biology 6. World Scientific, pp. 161-203. ISBN 9789814749329.

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    Abstract

    Small heat shock proteins (sHsps) are a diverse family evolved from ancient stress proteins that are now associated with protecting microbial, plant, worm, insect and mammalian cells under stress, where prevention of aggregation of destabilized proteins is considered to be their general function. The sequences all contain a short a-crystallin domain (ACD) bracketed by variable sequence extensions that contribute to a dynamic continuum of oligomeric forms. A few large symmetric oligomeric assemblies from nonmetazoans have been resolved by crystallography, as well as a few metazoan subassembly forms. A structure-based sequence alignment of the ACDs from resolved structures with representative sequences of sHsps from species of high economic, model or medical value is presented. The ACDs are portrayed to emphasize their interaction interfaces. The construction of a range of nanoassemblies from a polyvalent building block by binding IXI/V sequence motifs in extensions into partner ACD pockets is illustrated. This interaction mechanism can also be used to connect sHsps to energy driven chaperone machines, as shown for the interaction with cochaperone Bag3 in myofibril Z-disks. The resolved complete assemblies are built from a strand exchange dimer, whereas animal sHsps have an antiparallel (AP) dimer interface that forms a shared groove which can change shape. Spectroscopy has shown how the AP interface is regulated by pH. Animal sHsp full assemblies are undetermined, although some clues as to the structural role of the hydrophobic N-terminal extensions can be surmised from analysis of the resolved assemblies. A mechanism for prevention of protein aggregation is likely to involve a stress-regulated ensemble of interconverting destabilized sHsp assemblies when interfaces and extensions become more accessible to the proteome. Rapid developments in EM offer the possibility of resolution of an sHsp ensemble if the level of polydispersity can be lowered.

    Metadata

    Item Type: Book Section
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 18 Jul 2017 12:21
    Last Modified: 18 Jul 2017 12:21
    URI: http://eprints.bbk.ac.uk/id/eprint/19084

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