Sj. Kim et al., Crystal structure of proteolytic fragments of the redox-sensitive Hsp33 with constitutive chaperone activity, NAT ST BIOL, 8(5), 2001, pp. 459-466
Heat shock protein 33 (Hsp33) inhibits aggregation of partially denatured p
roteins during oxidative stress. The chaperone activity of Hsp33 is unique
among heat shock proteins because the activity is reversibly regulated by c
ellular redox status. We report here the crystal structure of the N-termina
l region of Hsp33 fragments with constitutive chaperone activity. The struc
ture reveals that the N-terminal portion of Hsp33 forms a tightly associate
d dimer formed by a domain crossover. A concave groove on the dimeric surfa
ce contains an elongated hydrophobic patch that could potentially bind dena
tured protein substrates. The termini of the subunits are located near the
hydrophobic patch, indicating that the cleaved C-terminal domain may shield
the hydrophobic patch in an inactive state. Two of the four conserved zinc
-coordinating cysteines are in the end of the N-terminal domain, and the ot
her two are in the cleaved C-terminal domain. The structural information an
d subsequent biochemical characterizations suggest that the redox switch of
Hsp33 occurrs by a reversible dissociation of the C-terminal regulatory do
main through oxidation of zinc-coordinating cysteines and zinc release.