2LSY

Structure of the C-terminal domain from human REV1

Summary for 2LSY

• Entry DOI: 10.2210/pdb2lsy/pdb
• Related: 2LSK
• NMR Information: BMRB: 18455
• Descriptor: DNA repair protein REV1 (1 entity in total)
• Functional Keywords: dna polymerase, translesion synthesis, dna repair, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): Q9UBZ9
• Total number of polymer chains: 1
• Total formula weight: 11011.67

Authors

Pozhidaeva, A.,Pustovalova, Y.,Bezsonova, I.,Korzhnev, D. (deposition date: 2012-05-09, release date: 2012-06-27, Last modification date: 2024-05-15)

Primary citation

Pozhidaeva, A.,Pustovalova, Y.,D'Souza, S.,Bezsonova, I.,Walker, G.C.,Korzhnev, D.M.
NMR structure and dynamics of the C-terminal domain from human Rev1 and its complex with Rev1 interacting region of DNA polymerase eta.
Biochemistry, 51:5506-5520, 2012

PubMed Abstract: Rev1 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 polη, ι, and κ to their cognate DNA lesions and facilitates their subsequent exchange to polζ that extends the distorted DNA primer-template. Rev1 interaction with the other major human TLS polymerases, polη, ι, κ, and the regulatory subunit Rev7 of polζ, 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 polη (residues 524-539). The domain forms a four-helix bundle with a well-structured N-terminal β-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 α-helix. NMR spin-relaxation and NMR relaxation dispersion measurements suggest that free Rev1-CT and Rev1-CT/polη-RIR complex exhibit μs-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.

PubMed: 22691049
DOI: 10.1021/bi300566z

Experimental method

SOLUTION NMR