2lsk
From Proteopedia
C-terminal domain of human REV1 in complex with DNA-polymerase H (eta)
Structural highlights
FunctionREV1_HUMAN Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.[1] [2] [3] [4] [5] Publication Abstract from PubMedRev1 is a translesion synthesis (TLS) DNA polymerase essential for DNA damage tolerance in eukaryotes. In the process of TLS stalled high-fidelity replicative DNA polymerases are temporarily replaced by specialized TLS enzymes that can bypass sites of DNA damage (lesions), thus allowing replication to continue or postreplicational gaps to be filled. Despite its limited catalytic activity, human Rev1 plays a key role in TLS by serving as a scaffold that provides an access of Y-family TLS polymerases poleta, iota, and kappa to their cognate DNA lesions and facilitates their subsequent exchange to polzeta that extends the distorted DNA primer-template. Rev1 interaction with the other major human TLS polymerases, poleta, iota, kappa and the regulatory subunit Rev7 of polzeta, is mediated by Rev1 C-terminal domain (Rev1-CT). We used NMR spectroscopy to determine the spatial structure of the Rev1-CT domain (residues 1157-1251) and its complex with Rev1 interacting region (RIR) from poleta (residues 524-539). The domain forms a four-helix bundle with a well-structured N-terminal beta-hairpin docking against helices 1 and 2, creating a binding pocket for the two conserved Phe residues of the RIR motif that upon binding folds into an alpha-helix. NMR spin-relaxation and NMR relaxation dispersion measurements suggest that free Rev1-CT and Rev1-CT/poleta-RIR complex exhibit mus-ms conformational dynamics encompassing the RIR binding site, which might facilitate selection of the molecular configuration optimal for binding. These results offer new insights into the control of TLS in human cells by providing a structural basis for understanding the recognition of the Rev1-CT by Y-family DNA polymerases. NMR Structure and Dynamics of the C-terminal Domain from Human Rev1 and its Complex with Rev1 Interacting Region of DNA Polymerase eta,Pozhidaeva A, Pustovalova Y, D'Souza S, Bezsonova I, Walker GC, Korzhnev DM Biochemistry. 2012 Jun 13. PMID:22691049[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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