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Crystal structure and assembly of a eukaryotic small heat shock protein

Abstract

The 2.7 Å structure of wheat HSP16.9, a member of the small heat shock proteins (sHSPs), indicates how its α-crystallin domain and flanking extensions assemble into a dodecameric double disk. The folding of the monomer and assembly of the oligomer are mutually interdependent, involving strand exchange, helix swapping, loose knots and hinged extensions. In support of the chaperone mechanism, the substrate-bound dimers, in temperature-dependent equilibrium with higher assembly forms, have unfolded N-terminal arms and exposed conserved hydrophobic binding sites on the α-crystallin domain. The structure also provides a model by which members of the sHSP protein family bind unfolded substrates, which are involved in a variety of neurodegenerative diseases and cataract formation.

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Figure 1: Sequence alignment and subunit exchange.
Figure 2: Assembly and fold of the wheat dodecamer.
Figure 3: Different chaperone assemblies but with the same fold.
Figure 4: Patching the α-crystallin domain and putative substrate binding sites.

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Acknowledgements

We are especially indebted to G. Lee and A. Basak, whose work on pea HSP18.1 provided the basis for these structural studies on the related wheat HSP16.9. We also acknowledge D. Moss, I. Tickle and H. Driessen for valuable discussions during the structure determination and O. Bateman for mass spectrometry measurements. We thank G. Leonard for his help during data collection, and staff at the ESRF, the EMBL outstation at DESY, Hamburg and of the CLRC of Daresbury Laboratory, Warrington, for their support of the work at those facilities. Research in the laboratory of E.V. was funded by grants from the National Institutes of Health and the U.S. Department of Agriculture (NRICGP). During preparation of this manuscript, E.V. is grateful for support from the National Science Foundation (POWRE Award), the Guggenheim Foundation and the Dutch National Science Foundation. Financial support of the Medical Research Council (London) to C.S. and R.v.M. is very gratefully acknowledged.

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Correspondence to Christine Slingsby.

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van Montfort, R., Basha, E., Friedrich, K. et al. Crystal structure and assembly of a eukaryotic small heat shock protein. Nat Struct Mol Biol 8, 1025–1030 (2001). https://doi.org/10.1038/nsb722

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