1. Physical Biosciences Division of the Lawrence Berkeley National Laboratory and the Department of Chemistry, University of California at Berkeley, 220 Melvin Calvin Laboratory, Berkeley, California 94720-5230, USA

Correspondence to: Sung-Hou Kim¹ Correspondence and requests for materials should be addressed to S.-H.K. (e-mail: Email: SHKIM@LBL.GOV).The identity code of the coordinates and structure factors are 1SHS and R1SHSSF,respectively, in the Brookhaven Protein Data Bank.

Abstract

The principal heat-shock proteins that have chaperone activity (that is, they protect newly made proteins from misfolding) belong to five conserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs can form large multimeric structures and have a wide range of cellular functions, including endowing cells with thermotolerance in vivo¹,² and being able to act as molecular chaperones in vitro^{3, 4, 5, 6, 7, 8}; sHSPs do this by forming stable complexes with folding intermediates of their protein substrates⁹,¹⁰. However, there is little information available about these structures or the mechanism by which substrates are protected from thermal denaturation by sHSPs. Here we report the crystal structure of a small heat-shock protein from Methanococcus jannaschii, a hyperthermophilic archaeon. The monomeric folding unit is a composite -sandwich in which one of the -strands comes from a neighbouring molecule. Twenty-four monomers form a hollow spherical complex of octahedral symmetry, with eight trigonal and six square 'windows'. The sphere has an outer diameter of 120 Å and an inner diameter of 65 Å.