Molecular Basis for Oligomeric-DNA Binding and Episome Maintenance by KSHV LANA

PLoS Pathogens

Ronen Marmorstein¹  Fang Lu¹  Horng-Shen Chen¹  Paul M. Lieberman¹  John F. Domsic¹ 

[1] Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America

关键词: DNA-binding proteins;    DNA replication;    Crystal structure;    DNA binding assay;    Dimers (Chemical physics);    Electrophoretic mobility shift assay;    DNA structure;    Cell binding assay;   

DOI  :  10.1371/journal.ppat.1003672

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

LANA is the KSHV-encoded terminal repeat binding protein essential for viral replication and episome maintenance during latency. We have determined the X-ray crystal structure of LANA C-terminal DNA binding domain (LANADBD) to reveal its capacity to form a decameric ring with an exterior DNA binding surface. The dimeric core is structurally similar to EBV EBNA1 with an N-terminal arm that regulates DNA binding and is required for replication function. The oligomeric interface between LANA dimers is dispensable for single site DNA binding, but is required for cooperative DNA binding, replication function, and episome maintenance. We also identify a basic patch opposite of the DNA binding surface that is responsible for the interaction with BRD proteins and contributes to episome maintenance function. The structural features of LANADBD suggest a novel mechanism of episome maintenance through DNA-binding induced oligomeric assembly.

【 授权许可】

CC BY