Structure-based mutational analysis of the bovine papillomavirus E1 helicase domain identifies residues involved in the nonspecific DNA binding activity required for double trimer formation

Liu, X., Schuck, S., Stenlund, A. (May 2010) Structure-based mutational analysis of the bovine papillomavirus E1 helicase domain identifies residues involved in the nonspecific DNA binding activity required for double trimer formation. J Virol, 84 (9). pp. 4264-4276. ISSN 1098-5514 (Electronic) 0022-538X (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/20147403
DOI: 10.1128/JVI.02214-09

Abstract

The papillomavirus E1 protein is a multifunctional initiator protein responsible for preparing the viral DNA template for initiation of DNA replication. The E1 protein encodes two DNA binding activities that are required for initiation of DNA replication. A well characterized sequence specific DNA binding activity resides in the E1 DBD and is used to tether E1 to the papillomavirus ori. A non-sequence specific DNA binding activity is additionally required for formation of the E1 double trimer (DT) complex, which is responsible for the local template melting that precedes loading of the E1 helicase. This DNA binding activity is very poorly understood. Here we use a structure-based mutagenesis approach to identify residues in the E1 helicase domain that are required for the non-sequence specific DNA binding and DT formation. We find that three groups of residues are involved in nonspecific DNA binding; the E1 beta-hairpin structure containing R505, K506 and H507, a hydrophobic loop containing F464, and a charged loop containing K461 together generate the binding surface involved in nonspecific DNA binding. These residues are well conserved in the T-antigens from the polyomaviruses indicating that the polyomaviruses share this non-specific DNA binding activity.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
organism description > virus
CSHL Authors:
Communities: CSHL labs > Stenlund lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: CSHL Librarian
Date: May 2010
Date Deposited: 03 Oct 2011 20:00
Last Modified: 30 Dec 2014 16:24
PMCID: PMC2863750
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15465

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