Mechanism of origin DNA recognition and assembly of an initiator-helicase complex by SV40 large tumor antigen.
PubMed id: 23545501
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.