title: Marching to the beat of the ring: polypeptide translocation by AAA+ proteases.
abstract: ATP-dependent proteases exist in all cells and are crucial regulators of the proteome. These machines consist of a hexameric, ring-shaped motor responsible for engaging, unfolding, and translocating protein substrates into an associated peptidase for degradation. Here, we discuss recent work that has established how the six motor subunits coordinate their ATP-hydrolysis and translocation activities. The closed topology of the ring and the rigidity of subunit/subunit interfaces cause conformational changes within a single subunit to drive motions in other subunits of the hexamer. This structural effect generates allostery between the ATP-binding sites, leading to a preferred order of binding and hydrolysis events among the motor subunits as well as a unique biphasic mechanism of translocation.
authors: QB3 Institute, University of California, Berkeley, CA 94720, USA; Biophysics Graduate Group, University of California, Berkeley, CA 94720, USA.
authors: Kristofor
authors: K
authors: Nyquist
authors: QB3 Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. Electronic address: a.martin@berkeley.edu.
authors: Andreas
authors: A
authors: Martin
mesh_terms: D049069:ATP-Dependent Proteases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000494:Allosteric Regulation; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008958:Models, Molecular; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D059748:Proteolysis
chemical_list: D029968:Escherichia coli Proteins; D021122:Protein Subunits; D000255:Adenosine Triphosphate; D049069:ATP-Dependent Proteases
keywords: AAA+ protease; ATP hydrolysis; protein translocation; subunit coordination