Next Article in Journal
Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System
Next Article in Special Issue
Virus Infection and Death Receptor-Mediated Apoptosis
Previous Article in Journal
Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import
Previous Article in Special Issue
The Bcl-2 Family in Host-Virus Interactions
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Viruses 2017, 9(10), 305; https://doi.org/10.3390/v9100305

Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 1 October 2017 / Revised: 15 October 2017 / Accepted: 18 October 2017 / Published: 20 October 2017
(This article belongs to the Special Issue Viral Infection and Apoptosis)
View Full-Text   |   Download PDF [6597 KB, uploaded 20 October 2017]   |  

Abstract

Programmed cell death or apoptosis is an important component of host defense systems against viral infection. The B-cell lymphoma 2 (Bcl-2) proteins family is the main arbiter of mitochondrially mediated apoptosis, and viruses have evolved sequence and structural mimics of Bcl-2 to subvert premature host cell apoptosis in response to viral infection. The sequencing of the canarypox virus genome identified a putative pro-survival Bcl-2 protein, CNP058. However, a role in apoptosis inhibition for CNP058 has not been identified to date. Here, we report that CNP058 is able to bind several host cell pro-death Bcl-2 proteins, including Bak and Bax, as well as several BH3 only-proteins including Bim, Bid, Bmf, Noxa, Puma, and Hrk with high to moderate affinities. We then defined the structural basis for CNP058 binding to pro-death Bcl-2 proteins by determining the crystal structure of CNP058 bound to Bim BH3. CNP058 adopts the conserved Bcl-2 like fold observed in cellular pro-survival Bcl-2 proteins, and utilizes the canonical ligand binding groove to bind Bim BH3. We then demonstrate that CNP058 is a potent inhibitor of ultraviolet (UV) induced apoptosis in a cell culture model. Our findings suggest that CNP058 is a potent inhibitor of apoptosis that is able to bind to BH3 domain peptides from a broad range of pro-death Bcl-2 proteins, and may play a key role in countering premature host apoptosis. View Full-Text
Keywords: poxvirus; avipoxvirus; apoptosis; X-ray crystallography; isothermal titration calorimetry; Bcl-2 poxvirus; avipoxvirus; apoptosis; X-ray crystallography; isothermal titration calorimetry; Bcl-2
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Anasir, M.I.; Baxter, A.A.; Poon, I.K.H.; Hulett, M.D.; Kvansakul, M. Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation of Apoptosis. Viruses 2017, 9, 305.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top