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Colin E. McVey Lab

Macromolecular Crystallography Unit

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Our research is focused on gammaherpesvirus viral modulation and the study of proteins encoded by herpesvirus to understand their structural and functional role in viral latency. Viral latency is the ability of a pathogenic virus to lie dormant within a cell. One of the most essential tasks during latency is to maintain the viral episome through cycles of mitotic cell divisions. The focal point of our research is LANA, a multifunctional protein that is critical for the establishment and maintenance of viral latency. My lab combines both biophysical (EMSA, ITC & Thermofluor) and structural methods (BioSAXS & X-ray crystallography) to understand protein interactions involved in viral latency and modulation of its host.

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Colin E. McVey
Principal Investigator
PhD in Chemistry, University of York, UK

Phone (+351) 214469663 | Extension 1663
mcvey@itqb.unl.pt | MX Unit Website

 

Research Interests

Establishment and maintenance of viral latency

Ongoing projects:

  • Structural basis of Viral TR DNA tethering by LANA
  • Mechanism of DNA cooperative binding and oligomerization by LANA
  • Structure and BioSAXS analysis of LANA complexes

Recruiting the EC5S-type ubiquitin ligase complex by gammaherpresvirus

We are studying the structural and functional of LANA in the recruitment of the EC5S E3 ubiquitin ligase complex to understand its role in NFκB and c-Myc modulation.

Ongoing projects:

  • Structure and characterization of the LANA EC5S E3 ubiquitin ligase complex

Signalosome assembly by Src homology domain interaction in gammaherpesvirus

We are studying the structural and functional role of M2 in B-cell activation. M2 seems to function predominantly as a scaffolding protein that forms multiprotein complexes mimicking or perpetuating signals from the BCR. Studies suggest that M2 forms a microsignalosome complex as it mediates the coordinated recruitment of intracellular effectors, such as the kinases Lyn and Syk, the adaptor Vav1, and phospholipase C-gamma2.

Ongoing projects:

  • Structure of the M2 signalosome complex

 

Group Members

    • Rajesh Ponnusamy, Post-doc
    • Bruno Correia, PhD student
    • Rute Chitas, Research assistant
    • Tânia Custódio, MSc Student

 

Selected Publications 

  1. KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat viral DNA: Nucleic Acids Research 2015

  2. Crystal Structure of the Gamma-2 Herpesvirus LANA DNA Binding Domain Identifies Charged Surface Residues Which Impact Viral Latency: PLoS Pathogens 2013

  3. Role of Src Homology Domain Binding in Signaling Complexes Assembled by the Murid gamma-Herpesvirus M2 Protein: Journal of Biological Chemistry 2013

 

Laboratory's Website

For further information please visit the Laboratory's Website

 

Virologia Estrutural (PT)

Unidade de Cristalografia de Macromoléculas

A investigação levada a cabo no Laboratório de Virologia Estrutural foca-se no estudo da modulação viral de gama-herpesvírus e das proteínas codificadas por herpesvírus, de modo a perceber o seu papel estrutural e funcional na latência viral (capacidade de um vírus patogénico permanecer latente numa célula). Uma das mais importantes tarefas durante a latência é a manutenção do epissoma viral ao longo dos ciclos de divisão mitótica da célula. O ponto principal de investigação deste laboratório é a proteína LANA, uma proteína multi-funcional que é importante no estabelecimento e manutenção da latência viral. Neste laboratório, utiliza-se uma combinação de métodos biofísicos (EMSA, ITC & Thermofluor) e estruturais (BioSAXS & Cristalografia de Raios-X) para compreender as interacções de proteínas envolvidas na latência viral e modulação do seu hospedeiro.

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