title: Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein.
abstract: AAA proteins remodel other proteins to affect a multitude of biological processes. Their power to remodel substrates must lie in their capacity to couple substrate binding to conformational changes via cycles of nucleotide binding and hydrolysis, but these relationships have not yet been deciphered for any member. We report that when one AAA protein, Hsp104, engages polypeptide at the C-terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2) drives a conformational change in the middle region. This, in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This interdomain communication pathway can be blocked by mutation in the middle region or bypassed by antibodies that bind there, demonstrating the crucial role this region plays in transducing signals from one end of the molecule to the other.
authors: Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
authors: Anil G
authors: AG
authors: Cashikar
authors: Eric C
authors: EC
authors: Schirmer
authors: Douglas A
authors: DA
authors: Hattendorf
authors: John R
authors: JR
authors: Glover
authors: Melarkode S
authors: MS
authors: Ramakrishnan
authors: Danielle M
authors: DM
authors: Ware
authors: Susan L
authors: SL
authors: Lindquist
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D000908:Antibodies, Fungal / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D004789:Enzyme Activation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D006868:Hydrolysis; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D011107:Polylysine; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases