CRYSTAL-STRUCTURE OF A SMALL HEAT-SHOCK-PROTEIN

The principal heat-shock proteins that have chaperone activity (that i s, they protect newly made proteins from misfolding) belong to five co nserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs can form large multimeric structures and h ave a wide range of cellular functions, including endowing cells with thermotolerance in vivo(1,2) and being able to act as molecular chaper ones in vitro(3-8); sHSPs do this by forming stable complexes with fol ding intermediates of their protein substrates(9,10). However, there i s 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 fr om Methanococcus jannaschii, a hyperthermophilic archaeon. The monomer ic folding unit is a composite beta-sandwich in which one of the beta- 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 Ang strom and an inner diameter of 65 Angstrom.