6e8d | pdb_00006e8d
Crystal structure of the Bacillus subtilis sliding clamp-MutL complex.
Structural highlights
Function[A0A085C685_BACIU] Confers DNA tethering and processivity to DNA polymerases and other proteins. Acts as a clamp, forming a ring around DNA (a reaction catalyzed by the clamp-loading complex) which diffuses in an ATP-independent manner freely and bidirectionally along dsDNA. Initially characterized for its ability to contact the catalytic subunit of DNA polymerase III (Pol III), a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria; Pol III exhibits 3'-5' exonuclease proofreading activity. The beta chain is required for initiation of replication as well as for processivity of DNA replication.[PIRNR:PIRNR000804] Publication Abstract from PubMedThe beta-clamp is a protein hub central to DNA replication and fork management. Proteins interacting with the beta-clamp harbor a conserved clamp-binding motif that is often found in extended regions. Therefore, clamp interactions have -almost exclusively- been studied using short peptides recapitulating the binding motif. This approach has revealed the molecular determinants that mediate the binding but cannot describe how proteins with clamp-binding motifs embedded in structured domains are recognized. The mismatch repair protein MutL has an internal clamp-binding motif, but its interaction with the beta-clamp has different roles depending on the organism. In Bacillus subtilis, the interaction stimulates the endonuclease activity of MutL and it is critical for DNA mismatch repair. Conversely, disrupting the interaction between Escherichia coli MutL and the beta-clamp only causes a mild mutator phenotype. Here, we determined the structures of the regulatory domains of E. coli and B. subtilis MutL bound to their respective beta-clamps. The structures reveal different binding modes consistent with the binding to the beta-clamp being a two-step process. Functional characterization indicates that, within the regulatory domain, only the clamp binding motif is required for the interaction between the two proteins. However, additional motifs beyond the regulatory domain may stabilize the interaction. We propose a model for the activation of the endonuclease activity of MutL in organisms lacking methyl-directed mismatch repair. Binding of the regulatory domain of MutL to the sliding beta-clamp is species specific.,Almawi AW, Scotland MK, Randall JR, Liu L, Martin HK, Sacre L, Shen Y, Pillon MC, Simmons LA, Sutton MD, Guarne A Nucleic Acids Res. 2019 Mar 27. pii: 5420525. doi: 10.1093/nar/gkz115. PMID:30916336[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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