8xla
From Proteopedia
Mismatch Repair Complex
Structural highlights
FunctionQ5FAJ1_NEIG1 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 PubMedMany prokaryotes, including members of the Neisseria species, lack MutH and cannot employ methyl-directed DNA mismatch repair (MMR). The nick on the daughter strand is created by the endonuclease activity present in the C-terminal domain (CTD) of the MutL homodimer. MutL-CTD is known to interact with the processivity-clamp. The crystal structure of the homodimeric MutL-CTD from Neisseria (NgoL-CTD) in complex with homodimeric processivity-clamp (Nbeta-Clamp) shows that each NgoL-CTD monomer binds to a Nbeta-Clamp monomer through the conserved motif III (517QHLLIP522). The structure and allied biochemical studies plus in vivo growth assays conducted with wild-type (wt) plus mutant proteins shows that the endonuclease dimer sits transversely across the C-terminal face of the Nbeta-Clamp ring. The comparison of the structure with that of the partial prokaryotic replisome suggests that the relative orientation of DNA, Nbeta-Clamp, and NgoL-CTD may direct the daughter strand towards one of the active sites in endonuclease homodimer. Nicking assays conducted with wt and mutant NgoL-CTD in the presence and absence of Nbeta-Clamp support this inference. Overall, our studies posit that strand discrimination in non-methyl-directed MMR is achieved through a structural strategy involving the beta-Clamp which is distinct from the chemical strategy employed in prokaryotes like Escherichia coli. The structure of the MutL-CTD:processivity-clamp complex provides insight regarding strand discrimination in non-methyl-directed DNA mismatch repair.,Nirwal S, Jha R, Narayanan N, Sharma M, Kulkarni DS, Sharma D, Babu AS, Suthar DK, Rao DN, Nair DT Nucleic Acids Res. 2025 Feb 8;53(4):gkaf094. doi: 10.1093/nar/gkaf094. PMID:39988319[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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