Leppard, Keith, Emmott, Edward, Cortese, Marc S. and Rich, Tina (2009) Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis. Journal of General Virology, Vol.90 (No.1). pp. 95-104. doi:10.1099/vir.0.005512-0 ISSN 0022-1317.

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Abstract

Human adenovirus type 5 infection causes the disruption of structures in the cell nucleus termed promyelocytic leukaemia (PML) protein nuclear domains or ND10, which contain the PML protein as a critical component. This disruption is achieved through the action of the viral E4 Orf3 protein, which forms track-like nuclear structures that associate with the PML protein. This association is mediated by a direct interaction of Orf3 with a specific PML isoform, PMLII. We show here that the Orf3 interaction properties of PMLII are conferred by a 40 aa residue segment of the unique C-terminal domain of the protein. This segment was sufficient to confer interaction on a heterologous protein. The analysis was informed by prior application of a bioinformatic tool for the prediction of potential protein interaction sites within unstructured protein sequences (predictors of naturally disordered region analysis; PONDR). This tool predicted three potential molecular recognition elements (MoRE) within the C-terminal domain of PMLII, one of which was found to form the core of the Orf3 interaction site, thus demonstrating the utility of this approach. The sequence of the mapped Orf3-binding site on PML protein was found to be relatively poorly conserved across other species; however, the overall organization of MoREs within unstructured sequence was retained, suggesting the potential for conservation of functional interactions.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Adenovirus diseases -- Research, Acute myeloid leukemia -- Research, Protein-protein interactions, Proteins -- Research
Journal or Publication Title:	Journal of General Virology
Publisher:	Society for General Microbiology
ISSN:	0022-1317
Official Date:	January 2009
Dates:	Date Event January 2009 Published
Volume:	Vol.90
Number:	No.1
Page Range:	pp. 95-104
DOI:	10.1099/vir.0.005512-0
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), American Institute for Cancer Research (AICR)

Data sourced from Thomson Reuters' Web of Knowledge

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