5D46

Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl Transferase: Implications for V(D)J Recombination

Summary for 5D46

• Entry DOI: 10.2210/pdb5d46/pdb
• Descriptor: Terminal deoxynucleotidyltransferase, DNA (5'-D(*AP*AP*AP*AP*AP*A)-3'), DNA (5'-D(*TP*TP*TP*TP*TP*GP*C)-3'), ... (9 entities in total)
• Functional Keywords: tdt, synapsis, double strand breaks, transferase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 5
• Total formula weight: 54105.82

Authors

Loc'h, J.,Rosario, S.,Delarue, M. (deposition date: 2015-08-07, release date: 2016-07-27, Last modification date: 2024-01-10)

Primary citation

Loc'h, J.,Rosario, S.,Delarue, M.
Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl Transferase: Implications for V(D)J Recombination.
Structure, 24:1452-1463, 2016

PubMed Abstract: Eukaryotic DNA polymerase of the polX family, such as pol μ and terminal deoxynucleotidyl transferase (TdT), are key components of the non-homologous end-joining or V(D)J recombination machinery, respectively. The established role of TdT is to add random nucleotides during V(D)J recombination. Here we show that TdT also has a templated-polymerase activity, similar to pol μ, in the presence of higher concentrations of a downstream DNA duplex, and performs a micro-homology single base-pair search to align the DNA synapsis. To understand the molecular basis of this alignment, we solve crystal structures of TdT with four DNA strands and study the influence of the 3' protruding end. Two mutations in TdT inspired by sequence alignments with pol μ further improve the templated activity. We propose that both templated and untemplated activities of TdT are needed to explain the distributions of lengths of N regions observed experimentally in T cell receptors and antibodies.

PubMed: 27499438
DOI: 10.1016/j.str.2016.06.014

Experimental method

X-RAY DIFFRACTION (2.8 Å)