title: Turned on for degradation: ATPase-independent degradation by ClpP.
abstract: Clp is a barrel-shaped hetero-oligomeric ATP-dependent protease comprising a hexameric ATPase (ClpX or ClpA) that unfolds protein substrates and translocates them into the central chamber of the tetradecameric proteolytic component (ClpP) where they are degraded processively to short peptides. Chamber access is controlled by the N-terminal 20 residues (for Escherichia coli) in ClpP that prevent entry of large polypeptides in the absence of the ATPase subunits and ATP hydrolysis. Remarkably, removal of 10-17 residues from the mature N-terminus allows processive degradation of a large model unfolded substrate to short peptides without the ATPase subunit or ATP hydrolysis; removal of 14 residues is maximal for activation. Furthermore, since the product size distribution of Delta14-ClpP is identical to ClpAP and ClpXP, the ATPases do not play an essential role in determining this distribution. Comparison of the structures of Delta14-ClpP and Delta17-ClpP with other published structures shows R15 and S16 are labile and that residue 17 can adopt a range of rotomers to ensure protection of a hydrophobic pocket formed by I19, R24 and F49 and maintain a hydrophilic character of the pore.
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, 17033, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bewley
authors.forename: Vito
authors.initials: V
authors.lastname: Graziano
authors.forename: Kathleen
authors.initials: K
authors.lastname: Griffin
authors.forename: John M
authors.initials: JM
authors.lastname: Flanagan
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry; D002364:Caseins / Q000737:chemistry; D020134:Catalytic Domain; D049071:Endopeptidase Clp / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D017353:Gene Deletion; D014644:Genetic Variation; D006868:Hydrolysis; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary
chemical_list: D002364:Caseins; D029968:Escherichia coli Proteins; D010455:Peptides; D000255:Adenosine Triphosphate; C483568:ClpA protease, E coli; C483572:ClpP protease, E coli; C483573:ClpXP protease, E coli; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases