title: Molecular basis for oligomeric-DNA binding and episome maintenance by KSHV LANA.
abstract: 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.
authors.affiliation: Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: Domsic
authors.forename: Horng-Shen
authors.initials: HS
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.forename: Ronen
authors.initials: R
authors.lastname: Marmorstein
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
mesh_terms: D000956:Antigens, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004261:DNA Replication; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen