Premium
SV40 Large T Antigen Helicase/Initiator Structure and Function
Author(s) -
Chen Xiaojiang,
Gai Dahai
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.492.3
Subject(s) - helicase , dna , dna replication , biophysics , biology , chemistry , duplex (building) , microbiology and biotechnology , biochemistry , rna , gene
SV40 replication system serves as a model system for studying DNA replication in eukaryotic cells. SV40 large T antigen (LTag) is a replicative helicase and a “pleiotropic” replication initiator that recognizes replication origin, and initiates origin DNA melting and unwinding. To understand how LTag assembles on origin DNA to initiate DNA melting/unwinding, we determined the structure of the LTag‐dsDNA‐ADP complex, which represents the first structure for a hexameric helicase/initiator bound to dsDNA in the central channel. This structure captures a distinctive intermediate complex corresponding to an early stage of SV40 origin unwinding. The LTag‐DNA‐ADP complex structure reveals several unexpected features regarding: i ) how a smaller hexameric channel accommodate a larger duplex DNA, ii ) how the six subunits of LTag in the channel interact with dsDNA, and iii ) how LTag distorts and melts the origin DNA using the β‐hairpin fingers and a nearby loop. I will present these new structural data and the implications for a plausible molecular mechanism for origin DNA melting and unwinding by this multi‐functional initiator and replicative helicase in eukaryotic cells.