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Large T antigen on the simian virus 40 origin of replication: a 3D snapshot prior to DNA replication
Author(s) -
GomezLorenzo Maria G.,
Valle Mikel,
Frank Joachim,
Gruss Claudia,
Sorzano Carlos Oscar S.,
Chen Xiaojiang S.,
Donate Luis Enrique,
Carazo Jose Maria
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg612
Subject(s) - biology , virology , snapshot (computer storage) , replication (statistics) , simian , dna replication , viral replication , dna , genetics , origin of replication , virus , computer science , operating system
Large T antigen is the replicative helicase of simian virus 40. Its specific binding to the origin of replication and oligomerization into a double hexamer distorts and unwinds dsDNA. In viral replication, T antigen acts as a functional homolog of the eukaryotic minichromosome maintenance factor MCM. T antigen is also an oncoprotein involved in transformation through interaction with p53 and pRb. We obtained the three‐dimensional structure of the full‐length T antigen double hexamer assembled at its origin of replication by cryoelectron microscopy and single‐particle reconstruction techniques. The double hexamer shows different degrees of bending along the DNA axis. The two hexamers are differentiated entities rotated relative to each other. Isolated strands of density, putatively assigned to ssDNA, protrude from the hexamer–hexamer junction mainly at two opposite sites. The structure of the T antigen at the origin of replication can be understood as a snapshot of the dynamic events leading to DNA unwinding. Based on these results a model for the initiation of simian virus 40 DNA replication is proposed.