title: Conformational stability of the full-atom hexameric model of the ClpB chaperone from Escherichia coli.
abstract: The Escherichia coli heat shock protein ClpB, a member of the Hsp100 family, plays a crucial role in cellular thermotolerance. In co-operation with the Hsp70 chaperone system, it is able to solubilize proteins aggregated by heat shock conditions and refold them into the native state in an ATP-dependent way. It was established that the mechanism of ClpB action depends on the formation of a ring-shaped hexameric structure and the translocation of a protein substrate through an axial channel. The structural aspects of this process are not fully known. By means of homology modeling and protein-protein docking, we obtained a model of the hexameric arrangement of the full-length ClpB protein complexed with ATP. A molecular dynamics simulation of this model was performed to assess its flexibility and conformational stability. The high mobility of the "linker" M-domain, essential for the renaturing activity of ClpB, was demonstrated, and the size and shape of central channel were analyzed. In this model, we propose the coordinates for a loop between b4 and B6 structural elements, not defined in previous structural research, which faces the inside of the channel and may therefore play a role in substrate translocation.
authors.affiliation: Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk, Kładki 24, Gdańsk 80-822, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Zietkiewicz
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Slusarz
authors.forename: Rafał
authors.initials: R
authors.lastname: Slusarz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Liberek
authors.forename: Sylwia
authors.initials: S
authors.lastname: Rodziewicz-Motowidło
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D049071:Endopeptidase Clp; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C069775:ClpB protein, E coli