Structural Analysis of E. coli hsp90 Reveals Dramatic Nucleotide-Dependent Conformational Rearrangements
| Autor: | Daniel R. Southworth, David A. Agard, Andrew K. Shiau, S.F. Harris |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Protein Folding Protein Conformation Adenylyl Imidodiphosphate Plasma protein binding Crystallography X-Ray General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Protein structure Nucleotide HSP90 Heat-Shock Proteins Binding site 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites biology Adenine Nucleotides Biochemistry Genetics and Molecular Biology(all) Escherichia coli Proteins Hsp90 Adenosine Diphosphate Microscopy Electron chemistry Biochemistry 030220 oncology & carcinogenesis Chaperone (protein) biology.protein Biophysics ADP binding Protein folding Dimerization Protein Binding |
| Zdroj: | Cell. 127(2):329-340 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2006.09.027 |
| Popis: | SummaryIn eukaryotes, the ubiquitous and abundant members of the 90 kilodalton heat-shock protein (hsp90) chaperone family facilitate the folding and conformational changes of a broad array of proteins important in cell signaling, proliferation, and survival. Here we describe the effects of nucleotides on the structure of full-length HtpG, the Escherichia coli hsp90 ortholog. By electron microscopy, the nucleotide-free, AMPPNP bound, and ADP bound states of HtpG adopt completely distinct conformations. Structural characterization of nucleotide-free and ADP bound HtpG was extended to higher resolution by X-ray crystallography. In the absence of nucleotide, HtpG exhibits an “open” conformation in which the three domains of each monomer present hydrophobic elements into the large cleft formed by the dimer. By contrast, ADP binding drives dramatic conformational changes that allow these hydrophobic elements to converge and shield each other from solvent, suggesting a mechanism by which nucleotides could control client protein binding and release. |
| Databáze: | OpenAIRE |
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