5b42
Crystal structure of the C-terminal endonuclease domain of Aquifex aeolicus MutL.Crystal structure of the C-terminal endonuclease domain of Aquifex aeolicus MutL.
Structural highlights
Function[MUTL_AQUAE] This protein is involved in the repair of mismatches in DNA. It is required for dam-dependent methyl-directed DNA mismatch repair. May act as a "molecular matchmaker", a protein that promotes the formation of a stable complex between two or more DNA-binding proteins in an ATP-dependent manner without itself being part of a final effector complex (By similarity). Publication Abstract from PubMedIn early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the beta-clamp-interacting motif (beta motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with beta-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until beta clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the beta motif. For example, the region corresponding to the beta motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the beta motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 A-resolution crystal structure of A. aeolicus MutL CTD, which lacks the beta motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of beta motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of beta-clamp and that beta-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a beta motif-containing MutL, required beta-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on beta-clamp. Structural Features and Functional Dependency on beta-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL.,Fukui K, Baba S, Kumasaka T, Yano T J Biol Chem. 2016 Aug 12;291(33):16990-7000. doi: 10.1074/jbc.M116.739664. Epub, 2016 Jul 1. PMID:27369079[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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