Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

被引：42

作者：

Chang, Y. Paul ^{[1
]}

Xu, Meng ^{[2
]}

Machado, Ana Carolina Dantas ^{[1
]}

Yu, Xian Jessica ^{[1
]}

Rohs, Remo ^{[1
,3
,4
,5
,6
]}

Chen, Xiaojiang S. ^{[1
,2
,3
,4
]}

机构：

[1] Univ So Calif, Mol & Computat Biol Program, Dept Biol Sci, Los Angeles, CA 90089 USA

[2] Univ So Calif, Grad Program Genet Mol & Cell Biol, Los Angeles, CA 90089 USA

[3] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA

[4] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA

[5] Univ So Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA

[6] Univ So Calif, Dept Comp Sci, Los Angeles, CA 90089 USA

来源：

CELL REPORTS | 2013年 / 3卷 / 04期

关键词：

SIMIAN-VIRUS-40 CORE ORIGIN; LARGE T-ANTIGEN; REPLICATIVE HEXAMERIC HELICASE; INTERFERON-BETA ENHANCER; STRUCTURAL BASIS; BINDING DOMAIN; PROTEIN; RESIDUES; HAIRPIN; ELECTROSTATICS;

D O I：

10.1016/j.celrep.2013.03.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1117 / 1127

页数：11

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