Crystal structure of a small heat-shock protein

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 β-sandwich in which one of the β-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.