The crystal structure of the carboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site.
Hsp90 is a ubiquitous, well-conserved molecular chaperone involved in the folding and stabilization of diverse proteins. Beyond its capacity for general protein folding, Hsp90 influences a wide array of cellular signaling pathways that underlie key biological and disease processes. It has been proposed that Hsp90 functions as a molecular clamp, dimerizing through its carboxy-terminal domain and utilizing ATP binding and hydrolysis to drive large conformational changes including transient dimerization of the amino-terminal and middle domains. We have determined the 2.6 A X-ray crystal structure of the carboxy-terminal domain of htpG, the Escherichia coli Hsp90. This structure reveals a novel fold and that dimerization is dependent upon the formation of a four-helix bundle. Remarkably, proximal to the helical dimerization motif, each monomer projects a short helix into solvent. The location, flexibility, and amphipathic character of this helix suggests that it may play a role in substrate binding and hence chaperone activity.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Seth F
SF
Harris
Andrew K
AK
Shiau
David A
DA
Agard
D000255:Adenosine Triphosphate / Q000737:chemistry; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D018841:HSP90 Heat-Shock Proteins; C489352:HtpG protein, E coli; C066720:HtpG protein, bacteria; D000255:Adenosine Triphosphate