2L0G

Solution NMR structure of ubiquitin-binding motif (UBM2) of human polymerase iota

Summary for 2L0G

• Entry DOI: 10.2210/pdb2l0g/pdb
• Related: 2L0F
• Descriptor: DNA polymerase iota (1 entity in total)
• Functional Keywords: translesion dna synthesis, dna polymerase iota, ubiquitin-binding motif, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9UNA4
• Total number of polymer chains: 1
• Total formula weight: 3736.21

Authors

Cui, G.,Benirschke, R.,Mer, G. (deposition date: 2010-07-01, release date: 2010-11-03, Last modification date: 2024-05-01)

Primary citation

Cui, G.,Benirschke, R.C.,Tuan, H.F.,Juranic, N.,Macura, S.,Botuyan, M.V.,Mer, G.
Structural Basis of Ubiquitin Recognition by Translesion Synthesis DNA Polymerase iota.
Biochemistry, 49:10198-10207, 2010

PubMed Abstract: Cells have evolved mutagenic bypass mechanisms that prevent stalling of the replication machinery at DNA lesions. This process, translesion DNA synthesis (TLS), involves switching from high-fidelity DNA polymerases to specialized DNA polymerases that replicate through a variety of DNA lesions. In eukaryotes, polymerase switching during TLS is regulated by the DNA damage-triggered monoubiquitylation of PCNA. How the switch operates is unknown, but all TLS polymerases of the so-called Y-family possess PCNA and ubiquitin-binding domains that are important for their function. To gain insight into the structural mechanisms underlying the regulation of TLS by ubiquitylation, we have probed the interaction of ubiquitin with a conserved ubiquitin-binding motif (UBM2) of Y-family polymerase Polι. Using NMR spectroscopy, we have determined the structure of a complex of human Polι UBM2 and ubiquitin, revealing a novel ubiquitin recognition fold consisting of two α-helices separated by a central trans-proline residue conserved in all UBMs. We show that, different from the majority of ubiquitin complexes characterized to date, ubiquitin residue Ile44 only plays a modest role in the association of ubiquitin with Polι UBM2. Instead, binding of UBM2 is centered on the recognition of Leu8 in ubiquitin, which is essential for the interaction.

PubMed: 21049971
DOI: 10.1021/bi101303t

Experimental method

SOLUTION NMR