title: Nucleotide-dependent conformational changes in a protease-associated ATPase HsIU.
abstract: BACKGROUND
  The bacterial heat shock locus ATPase HslU is an AAA(+) protein that has structures known in many nucleotide-free and -bound states. Nucleotide is required for the formation of the biologically active HslU hexameric assembly. The hexameric HslU ATPase binds the dodecameric HslV peptidase and forms an ATP-dependent HslVU protease.
  
  
  RESULTS
  We have characterized four distinct HslU conformational states, going sequentially from open to closed: the empty, SO(4), ATP, and ADP states. The nucleotide binds at a cleft formed by an alpha/beta domain and an alpha-helical domain in HslU. The four HslU states differ by a rotation of the alpha-helical domain. This classification leads to a correction of nucleotide identity in one structure and reveals the ATP hydrolysis-dependent structural changes in the HslVU complex, including a ring rotation and a conformational change of the HslU C terminus. This leads to an amended protein unfolding-coupled translocation mechanism.
  
  
  CONCLUSIONS
  The observed nucleotide-dependent conformational changes in HslU and their governing principles provide a framework for the mechanistic understanding of other AAA(+) proteins.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA. wang@mail.csb.yale.edu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Song
authors.forename: I S
authors.initials: IS
authors.lastname: Seong
authors.forename: M C
authors.initials: MC
authors.lastname: Franklin
authors.forename: S
authors.initials: S
authors.lastname: Kamtekar
authors.forename: S H
authors.initials: SH
authors.lastname: Eom
authors.forename: C H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D049069:ATP-Dependent Proteases; D000227:Adenine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000737:chemistry / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D001692:Biological Transport; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006835:Hydrazones / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D012697:Serine Endopeptidases
chemical_list: C097674:4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone; D000227:Adenine Nucleotides; D006360:Heat-Shock Proteins; D006835:Hydrazones; D010636:Phenols; D000244:Adenosine Diphosphate; D010450:Endopeptidases; D049069:ATP-Dependent Proteases; D012697:Serine Endopeptidases; D000251:Adenosine Triphosphatases