3mt6 | pdb_00003mt6
Structure of ClpP from Escherichia coli in complex with ADEP1
Structural highlights
FunctionCLPP_ECOLI Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. May play the role of a master protease which is attracted to different substrates by different specificity factors such as ClpA or ClpX. Publication Abstract from PubMedIn ClpXP and ClpAP complexes, ClpA and ClpX use the energy of ATP hydrolysis to unfold proteins and translocate them into the self-compartmentalized ClpP protease. ClpP requires the ATPases to degrade folded or unfolded substrates, but binding of acyldepsipeptide antibiotics (ADEPs) to ClpP bypasses this requirement with unfolded proteins. We present the crystal structure of Escherichia coli ClpP bound to ADEP1 and report the structural changes underlying ClpP activation. ADEP1 binds in the hydrophobic groove that serves as the primary docking site for ClpP ATPases. Binding of ADEP1 locks the N-terminal loops of ClpP in a beta-hairpin conformation, generating a stable pore through which extended polypeptides can be threaded. This structure serves as a model for ClpP in the holoenzyme ClpAP and ClpXP complexes and provides critical information to further develop this class of antibiotics. Acyldepsipeptide antibiotics induce the formation of a structured axial channel in ClpP: A model for the ClpX/ClpA-bound state of ClpP.,Li DH, Chung YS, Gloyd M, Joseph E, Ghirlando R, Wright GD, Cheng YQ, Maurizi MR, Guarne A, Ortega J Chem Biol. 2010 Sep 24;17(9):959-69. PMID:20851345[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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