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Publication Abstract from PubMed

Tyrosine recombinases are conserved in the three kingdoms of life. Here we present the first crystal structure of a full-length archaeal tyrosine recombinase, XerA from Pyrococcus abyssi, at 3.0 A resolution. In the absence of DNA substrate XerA crystallizes as a dimer where each monomer displays a tertiary structure similar to that of DNA-bound Tyr-recombinases. Active sites are assembled in the absence of dif except for the catalytic Tyr, which is extruded and located equidistant from each active site within the dimer. Using XerA active site mutants we demonstrate that XerA follows the classical cis-cleavage reaction, suggesting rearrangements of the C-terminal domain upon DNA binding. Surprisingly, XerA C-terminal alphaN helices dock in cis in a groove that, in bacterial tyrosine recombinases, accommodates in trans alphaN helices of neighbour monomers in the Holliday junction intermediates. Deletion of the XerA C-terminal alphaN helix does not impair cleavage of suicide substrates but prevents recombination catalysis. We propose that the enzymatic cycle of XerA involves the switch of the alphaN helix from cis to trans packing, leading to (i) repositioning of the catalytic Tyr in the active site in cis and (ii) dimer stabilisation via alphaN contacts in trans between monomers.

The carboxy-terminal alphaN helix of the archaeal XerA tyrosine recombinase is a molecular switch to control site-specific recombination.,Serre MC, El Arnaout T, Brooks MA, Durand D, Lisboa J, Lazar N, Raynal B, van Tilbeurgh H, Quevillon-Cheruel S PLoS One. 2013 May 7;8(5):e63010. doi: 10.1371/journal.pone.0063010. Print 2013. PMID:23667562^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.