Structural highlights
Function
PARC_ECOLI Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule. MukB stimulates the relaxation activity of topoisomerase IV and also has a modest effect on decatenation.[1] [2] [3] [4]
Publication Abstract from PubMed
Chromosome partitioning in Escherichia coli is assisted by two interacting proteins, topoisomerase (topo) IV and MukB. MukB stimulates the relaxation of negative supercoils by topo IV; to understand the mechanism of their action and to define this functional interplay, we determined the crystal structure of a minimal MukB-topo IV complex to 2.3 A resolution. The structure shows that the so-called 'hinge' region of MukB forms a heterotetrameric assembly with a C-terminal DNA binding domain (CTD) on topo IV's ParC subunit. Biochemical studies show that the hinge stimulates topo IV by competing for a site on the CTD that normally represses activity on negatively supercoiled DNA, while complementation tests using mutants implicated in the interaction reveal that the cellular dependency on topo IV derives from a joint need for both strand passage and MukB binding. Interestingly, the configuration of the MukB.topo IV complex sterically disfavours intradimeric interactions, indicating that the proteins may form oligomeric arrays with one another, and suggesting a framework by which MukB and topo IV may collaborate during daughter chromosome disentanglement.
Structural basis for the MukB-topoisomerase IV interaction and its functional implications in vivo.,Vos SM, Stewart NK, Oakley MG, Berger JM EMBO J. 2013 Oct 4. doi: 10.1038/emboj.2013.218. PMID:24097060[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li Y, Stewart NK, Berger AJ, Vos S, Schoeffler AJ, Berger JM, Chait BT, Oakley MG. Escherichia coli condensin MukB stimulates topoisomerase IV activity by a direct physical interaction. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18832-7. doi:, 10.1073/pnas.1008678107. Epub 2010 Oct 4. PMID:20921377 doi:http://dx.doi.org/10.1073/pnas.1008678107
- ↑ Hiasa H. The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions. Biochemistry. 2002 Oct 1;41(39):11779-85. PMID:12269820
- ↑ Pitts SL, Liou GF, Mitchenall LA, Burgin AB, Maxwell A, Neuman KC, Osheroff N. Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV. Nucleic Acids Res. 2011 Jun;39(11):4808-17. doi: 10.1093/nar/gkr018. Epub 2011, Feb 7. PMID:21300644 doi:http://dx.doi.org/10.1093/nar/gkr018
- ↑ Corbett KD, Schoeffler AJ, Thomsen ND, Berger JM. The structural basis for substrate specificity in DNA topoisomerase IV. J Mol Biol. 2005 Aug 19;351(3):545-61. PMID:16023670 doi:10.1016/j.jmb.2005.06.029
- ↑ Vos SM, Stewart NK, Oakley MG, Berger JM. Structural basis for the MukB-topoisomerase IV interaction and its functional implications in vivo. EMBO J. 2013 Oct 4. doi: 10.1038/emboj.2013.218. PMID:24097060 doi:http://dx.doi.org/10.1038/emboj.2013.218
