Correction: Structural Based Analyses of the JC Virus T-Antigen F258L Mutant Provides Evidence for DNA Dependent Conformational Changes in the C-Termini of Polyomavirus Origin Binding Domains

The replication of human polyomavirus JCV, which causes Progressive Multifocal Leukoen-cephalopathy, is initiated by the virally encoded T-antigen (Tag). The structure of the JC virus Tag origin-binding domain (OBD) was recently solved by X-ray crystallography. This structure revealed that the OBD contains a C-terminal pocket, and that residues from the multifunctional A1 and B2 motifs situated on a neighboring OBD molecule dock into the pocket. Related studies established that a mutation in a pocket residue (F258L) rendered JCV Tag unable to support JCV DNA replication. To establish why this mutation inactivated JCV Tag , we have solved the structure of the F258L JCV Tag OBD mutant. Based on this structure, it is concluded that the structural consequences of the F258L mutation are limited to the pocket region. Further analyses, utilizing the available polyomavirus OBD structures, indicate that the F258 region is highly dynamic and that the relative positions of F258 are governed by DNA binding. The possible functional consequences of the DNA dependent rearrangements, including promotion of OBD cycling at the replication fork, are discussed. A conserved feature of Polyomavirus T-antigens is a phenylalanine situated at the C-termini of their origin-binding domains (OBDs). Using the T-antigen encoded by JC virus, we have investigated why this residue is critical for viral DNA replication. The studies presented herein establish that the consequences of this mutation are limited to the interface formed by the docking of the phenylalanine containing C-terminal pocket region of the Copyright: © 2016 Meinke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. OBD with the multifunctional A1/B2 region. Related studies indicate that the conforma-tion of the C-terminal region of the OBD is altered by DNA binding. These observations suggest a model whereby cycling of the OBDs within the hexameric spiral structure at the replication fork is promoted by DNA binding.