Séminaire du lundi 11 avril 2011 à 14h30

 "Three-dimensional structures of viruses from cryo-electron microscopy: image analysis challenges".

Giovanni Cardone (NIH, Bethesda, MD, USA), Candidat pour un poste de chargé de recherche dans l'équipe "Structure et dynamique de protéines"

Salle de conférence (401),

Tour 23, Couloir 22-23,

4ème étage

Cryo-electron microscopy has long been one of most valuable techniques to explore the structure of large macromolecular complexes such as viruses. Combined with image processing, it allows the generation of three-dimensional structures that can be analyzed to understand many aspects of viral life cycles. Averaging methods like single particle analysis are very powerful to investigate the structure of viruses, or subcomponents of them, that display some level of internal symmetry. In the last two decades the development of efficient algorithms has led to the reconstruction of viral architectures at subnanometer resolution, and novel hybrid approaches have helped to interpret subunits arrangements at atomic resolution. More recently, technical advancements in electron tomography have opened a window on all the viruses lacking intrinsic symmetry, such as many enveloped viruses.

In this talk I will review my work on combining cryo-EM and image processing to study the ultrastructure of Influenza A virus, Herpes Simplex Virus and Rous Sarcoma Virus CA protein. Emphasis will be on the computational challenges encountered during their analysis, and the strategies developed or adopted to overcome them.

References:

- A.C. Steven, G. Cardone, C. Butan, D.C. Winkler and J.B. Heymann, "Three-dimensional Structures of Pleiomorphic Viruses from Cryo-Electron Tomography", in: M. Agbandje-McKenna, R. McKenna (Eds.), Structural Virology, RSC (2010).

- G. Cardone, J.G. Purdy, N. Cheng, R.C. Craven and A.C. Steven, “Visualization of a missing link in retrovirus capsid assembly”, Nature, 457, 694-698 (2009).

- B.L. Trus*, W.W. Newcomb*, N. Cheng*, G. Cardone*, L. Marekov, F.L. Homa, J.C. Brown and A.C. Steven, *joint first autorship “Allosteric signaling and a nuclear exit strategy: binding of UL25/UL17 heterodimers to DNA-filled HSV-1 capsids”, Molecular Cell, 26, 479-489 (2007).

- G. Cardone, D. Winkler, B.L. Trus, N. Cheng, J.E. Heuser, W.W. Newcomb, J.C. Brown and A.C. Steven, “Visualization of the herpes simplex virus portal in situ by cryo-electron tomography”, Virology, 361, 426-434 (2007).

- A. Harris*, G. Cardone*, D. Winkler, J.B. Heymann, M. Brecher, J.M. White and A.C. Steven, *joint first autorship, “Influenza virus pleiomorphy characterized by cryoelectron tomography”, Proceedings of the National Academy of Sciences, 103, 19123-7 (2006).