title: Mechanism of origin DNA recognition and assembly of an initiator-helicase complex by SV40 large tumor antigen.
abstract: The DNA tumor virus Simian virus 40 (SV40) is a model system for studying eukaryotic replication. SV40 large tumor antigen (LTag) is the initiator/helicase that is essential for genome replication. LTag recognizes and assembles at the viral replication origin. We determined the structure of two multidomain LTag subunits bound to origin DNA. The structure reveals that the origin binding domains (OBDs) and Zn and AAA+ domains are involved in origin recognition and assembly. Notably, the OBDs recognize the origin in an unexpected manner. The histidine residues of the AAA+ domains insert into a narrow minor groove region with enhanced negative electrostatic potential. Computational analysis indicates that this region is intrinsically narrow, demonstrating the role of DNA shape readout in origin recognition. Our results provide important insights into the assembly of the LTag initiator/helicase at the replication origin and suggest that histidine contacts with the minor groove serve as a mechanism of DNA shape readout.
authors.affiliation: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Y Paul
authors.initials: YP
authors.lastname: Chang
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.forename: Ana Carolina Dantas
authors.initials: AC
authors.lastname: Machado
authors.forename: Xian Jessica
authors.initials: XJ
authors.lastname: Yu
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.forename: Xiaojiang S
authors.initials: XS
authors.lastname: Chen
mesh_terms: D000957:Antigens, Viral, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004261:DNA Replication; D019281:Dimerization; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018741:Replication Origin; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D000957:Antigens, Viral, Tumor; D006639:Histidine; D004247:DNA; D004265:DNA Helicases
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