| Structural highlights
4u0g is a 42 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| NonStd Res: | , , , |
| Gene: | clpP2, Rv2460c, MTV008.16c (MYCTU), clpP1, clpP, Rv2461c, MTV008.17c (MYCTU) |
| Activity: | Endopeptidase Clp, with EC number 3.4.21.92 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CLPP2_MYCTU] 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 (By similarity). Degrades anti-sigma-D factor RsdA when present in a complex with ClpP1 and ClpX. Degrades anti-sigma-E factor RseA in the presence of ClpC1. Does not seem to act on anti-sigma-L factor RslA.[HAMAP-Rule:MF_00444][1] [2] [CLPP1_MYCTU] 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 (By similarity).
Publication Abstract from PubMed
Caseinolytic peptidase P (ClpP), a double-ring peptidase with 14 subunits, collaborates with ATPases associated with diverse activities (AAA+) partners to execute ATP-dependent protein degradation. Although many ClpP enzymes self-assemble into catalytically active homo-tetradecamers able to cleave small peptides, the Mycobacterium tuberculosis enzyme consists of discrete ClpP1 and ClpP2 heptamers that require a AAA+ partner and protein-substrate delivery or a peptide agonist to stabilize assembly of the active tetradecamer. Here, we show that cyclic acyldepsipeptides (ADEPs) and agonist peptides synergistically activate ClpP1P2 by mimicking AAA+ partners and substrates, respectively, and determine the structure of the activated complex. Our studies establish the basis of heteromeric ClpP1P2 assembly and function, reveal tight coupling between the conformations of each ring, show that ADEPs bind only to one ring but appear to open the axial pores of both rings, provide a foundation for rational drug development, and suggest strategies for studying the roles of individual ClpP1 and ClpP2 rings in Clp-family proteolysis.
Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery.,Schmitz KR, Carney DW, Sello JK, Sauer RT Proc Natl Acad Sci U S A. 2014 Sep 29. pii: 201417120. PMID:25267638[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Barik S, Sureka K, Mukherjee P, Basu J, Kundu M. RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis. Mol Microbiol. 2010 Feb;75(3):592-606. doi: 10.1111/j.1365-2958.2009.07008.x., Epub 2009 Dec 16. PMID:20025669 doi:http://dx.doi.org/10.1111/j.1365-2958.2009.07008.x
- ↑ Jaiswal RK, Prabha TS, Manjeera G, Gopal B. Mycobacterium tuberculosis RsdA provides a conformational rationale for selective regulation of sigma-factor activity by proteolysis. Nucleic Acids Res. 2013 Jan 11. PMID:23314154 doi:http://dx.doi.org/10.1093/nar/gks1468
- ↑ Schmitz KR, Carney DW, Sello JK, Sauer RT. Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery. Proc Natl Acad Sci U S A. 2014 Sep 29. pii: 201417120. PMID:25267638 doi:http://dx.doi.org/10.1073/pnas.1417120111
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