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7vuk

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Crystal Structure of the core region of Thermus thermophilus MutS2 complexed with ADP.

Structural highlights

7vuk is a 2 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.38Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MUTS2_THET8 Endonuclease that is involved in the suppression of homologous recombination and may therefore have a key role in the control of bacterial genetic diversity. Cleaves the phosphate backbone of oligodeoxynucleotides non-sequence-specifically at the 3' side of the phosphates. Preferably incises the branched DNA structures, especially the D-loop structure over the Holliday junction. Has ATPase activity. Binds to dsDNA but not to ssDNA.[HAMAP-Rule:MF_00092]^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

MutS family proteins are classified into MutS-I and -II lineages: MutS-I recognizes mismatched DNA and initiates mismatch repair, whereas MutS-II recognizes DNA junctions to modulate recombination. MutS-I forms dimeric clamp-like structures enclosing the mismatched DNA, and its composite ATPase sites regulate DNA-binding modes. Meanwhile, the structures of MutS-II have not been determined; accordingly, it remains unknown how MutS-II recognizes DNA junctions and how nucleotides control DNA binding. Here, we solved the ligand-free and ADP-bound crystal structures of bacterial MutS2 belonging to MutS-II. MutS2 also formed a dimeric clamp-like structure with composite ATPase sites. The ADP-bound MutS2 was more flexible compared to the ligand-free form and could be more suitable for DNA entry. The inner hole of the MutS2 clamp was two times larger than that of MutS-I, and site-directed mutagenesis analyses revealed DNA-binding sites at the inner hole. Based on these, a model is proposed that describes how MutS2 recognizes DNA junctions.

Structural and functional insights into the mechanism by which MutS2 recognizes a DNA junction.,Fukui K, Inoue M, Murakawa T, Baba S, Kumasaka T, Yano T Structure. 2022 Jul 7;30(7):973-982.e4. doi: 10.1016/j.str.2022.03.014. Epub 2022, Apr 18. PMID:35439431^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fukui K, Masui R, Kuramitsu S. Thermus thermophilus MutS2, a MutS paralogue, possesses an endonuclease activity promoted by MutL. J Biochem. 2004 Mar;135(3):375-84. PMID:15113836
↑ Fukui K, Kosaka H, Kuramitsu S, Masui R. Nuclease activity of the MutS homologue MutS2 from Thermus thermophilus is confined to the Smr domain. Nucleic Acids Res. 2007;35(3):850-60. Epub 2007 Jan 10. PMID:17215294 doi:http://dx.doi.org/10.1093/nar/gkl735
↑ Fukui K, Takahata Y, Nakagawa N, Kuramitsu S, Masui R. Analysis of a nuclease activity of catalytic domain of Thermus thermophilus MutS2 by high-accuracy mass spectrometry. Nucleic Acids Res. 2007;35(15):e100. Epub 2007 Aug 7. PMID:17686785 doi:http://dx.doi.org/10.1093/nar/gkm575
↑ Fukui K, Nakagawa N, Kitamura Y, Nishida Y, Masui R, Kuramitsu S. Crystal structure of MutS2 endonuclease domain and the mechanism of homologous recombination suppression. J Biol Chem. 2008 Nov 28;283(48):33417-27. Epub 2008 Oct 6. PMID:18838375 doi:10.1074/jbc.M806755200
↑ Fukui K, Inoue M, Murakawa T, Baba S, Kumasaka T, Yano T. Structural and functional insights into the mechanism by which MutS2 recognizes a DNA junction. Structure. 2022 Jul 7;30(7):973-982.e4. doi: 10.1016/j.str.2022.03.014. Epub 2022, Apr 18. PMID:35439431 doi:http://dx.doi.org/10.1016/j.str.2022.03.014