Crystal structure of proteolytic fragments of the redox-sensitive Hsp33 with constitutive chaperone activity

Citation
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
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NATURE STRUCTURAL BIOLOGY
ISSN journal
1072-8368 → ACNP
Volume
8
Issue
5
Year of publication
2001
Pages
459 - 466
Database
ISI
SICI code
1072-8368(200105)8:5<459:CSOPFO>2.0.ZU;2-T
Abstract
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.