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bioRxiv · 10.1101/2021.12.20.473600

High-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1

Horton, N.·Sanchez, J. L.·Ghadirian, N.
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Abstract

Two new structures of the N-terminal domain of the main replication protein, NS1, of Human Parvovirus B19 (B19V) are presented. This domain (NS1-nuc) plays an important role in the "rolling hairpin" replication of the single-stranded B19V DNA genome, recognizing origin of replication sequences in double-stranded DNA, and cleaving (i.e. nicking) single-stranded DNA at a nearby site known as the trs. One structure of NS1-nuc is solved to 2.4 [A] and shows the positions of two bound phosphate ions. A second structure shows the position of a single divalent cation in the DNA nicking active site. The threedimensional structure of NS1-nuc is well conserved between the two forms, as well as with a previously solved structure of a sequence variant of the same domain, however shown here at significantly higher resolution. Using structures of NS1-nuc homologues bound to single- and double-stranded DNA, models for DNA recognition and nicking by B19V NS1-nuc are presented which predict residues important for DNA cleavage and for sequence specific recognition at the viral origin of replication.

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Horton, N., Sanchez, J. L., Ghadirian, N.. 2021-12-21. High-Resolution Structure of the Nuclease Domain of the Human Parvovirus B19 Main Replication Protein NS1. https://doi.org/10.1101/2021.12.20.473600

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