Structural insights into the promiscuous DNA binding and broad substrate selectivity of fowlpox virus resolvase

Li, Na; Shi, Ke; Rao, Timsi; Banerjee, Surajit; Aihara, Hideki

doi:10.1038/s41598-019-56825-w

Title: Structural insights into the promiscuous DNA binding and broad substrate selectivity of fowlpox virus resolvase

Journal Article · 14 January 2020 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-019-56825-w · OSTI ID:1593448

Li, Na ^[1]; Shi, Ke ^[2]; Rao, Timsi ^[2]; Banerjee, Surajit ^[2];

^[2]

Henan Univ. of Technology, Zhengzhou (China); Univ. of Minnesota, Minneapolis, MN (United States)
Univ. of Minnesota, Minneapolis, MN (United States)

Fowlpox virus resolvase (Fpr) is an endonuclease that cleaves a broad range of branched DNA structures, including the Holliday junction (HJ), with little sequence-specificity. To better understand the mechanisms underlying its relaxed substrate specificity, we determined the crystal structures of Fpr and that in a novel complex with HJ at 3.1-Å resolution. In the Fpr-HJ complex, two Fpr dimers use several distinct regions to interact with different DNA structural motifs, showing versatility in DNA-binding. Biochemical and solution NMR data support the existence of non-canonical modes of HJ interaction in solution. The binding of Fpr to various DNA motifs are mediated by its flat DNA-binding surface, which is centered on a short loop spanning K61 to I72 and flanked by longer α-helices at the outer edges, and basic side grooves near the dimer interface. Replacing the Fpr loop K61~I72 with a longer loop from Thermus thermophilus RuvC (E71~A87) endows Fpr with an enhanced selectivity toward HJ cleavage but with a target sequence preference distinct from that of RuvC, highlighting a unique role of this loop region in Fpr-HJ interaction. Our work helps explain the broad substrate selectivity of Fpr and suggests a possible mode of its association with poxvirus hairpin telomeres.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: NIH-ORIP HEI; National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1593448

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 10; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
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Mutants of phage bIL67 RuvC with enhanced Holliday junction binding selectivity and resolution symmetry: DNA branch discrimination by a phage RuvC resolving enzyme Green, Victoria; Curtis, Fiona A.; Sedelnikova, Svetlana Molecular Microbiology, Vol. 89, Issue 6 https://doi.org/10.1111/mmi.12343	journal	August 2013
Replication and resolution of cloned poxvirus telomeres in vivo generates linear minichromosomes with intact viral hairpin termini. DeLange, A. M.; Reddy, M.; Scraba, D. Journal of Virology, Vol. 59, Issue 2 https://doi.org/10.1128/JVI.59.2.249-259.1986	journal	January 1986
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