Mutations in Sensor 1 and Walker B in the bovine papillomavirus E1 initiator protein mimic the nucleotide bound state

Liu, X., Stenlund, A. (February 2010) Mutations in Sensor 1 and Walker B in the bovine papillomavirus E1 initiator protein mimic the nucleotide bound state. Journal of Virology, 84 (4). pp. 1912-1919. ISSN 0022-538X

URL: http://www.ncbi.nlm.nih.gov/pubmed/19939914
DOI: 10.1128/JVI.01756-09

Abstract

Viral replication initiator proteins are multifunctional proteins that utilize ATP binding and hydrolysis by their AAA+ modules for multiple functions in the replication of their viral genomes. These proteins are therefore of particular interest for understanding how AAA+ proteins carry out multiple ATP driven functions. We have performed a comprehensive mutational analysis of the residues involved in ATP binding and hydrolysis in the papillomavirus E1 initiator protein based on the recent structural data. Ten of the 11 residues that were targeted were defective for ATP hydrolysis and seven of these were also defective for ATP binding. The three mutants that could still bind nucleotide represent the Walker B motif (D478, D479) and Sensor 1 (N523), three residues that are in close proximity to each other and generally are considered to be involved in ATP hydrolysis. Surprisingly however, two of these mutants, D478A and N523A, mimicked the nucleotide bound state and were capable of binding DNA in the absence of nucleotide. However, these mutants could not form the E1 double trimer (DT) in the absence of nucleotide, demonstrating that there are two qualitatively different consequences of ATP binding by E1, one which can be mimicked by D478A and N523A and one which cannot.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
organism description > virus > papillomavirus
CSHL Authors:
Communities: CSHL labs > Stenlund lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Brian Soldo
Date: 25 February 2010
Date Deposited: 14 Mar 2012 15:37
Last Modified: 30 Dec 2014 16:22
PMCID: PMC2812389
Related URLs:
URI: https://repository.cshl.edu/id/eprint/25175

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