Open AccessMolecular Basis for Oligomeric-DNA Binding and Episome Maintenance by KSHV LANA
Author(s) -
John F. Domsic,
Horng-Shen Chen,
Fang Lü,
Ronen Marmorstein,
Paul M. Lieberman
Publication year - 2013
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1003672
Subject(s) - dna , dna binding protein , biology , replication protein a , dna replication , origin recognition complex , microbiology and biotechnology , hmg box , dna binding domain , dna repair , genetics , eukaryotic dna replication , gene , transcription factor
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 (LANA DBD ) 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 LANA DBD suggest a novel mechanism of episome maintenance through DNA-binding induced oligomeric assembly.