Zihe Rao (Tsinghua University)
October 16, 2018 -
2:00 pm to 3:00 pm
Schultz Laboratory 107
Prof. Rao is a Biophysicist and Structural Biologist, mainly engaged in the study of crystal or CryoEM structures of proteins and pathogens related to human infection, as well as in the development of innovative drug treatment. To date, Prof Rao has published 335 peer-reviewed papers in international scientific journals with over 12,000 citations.
Since 2003, Prof. Rao has been elected as a Member of Chinese Academy of Sciences, Member of Academy of Sciences for Developing Countries, Fellow of Hertford College, University of Oxford, Member of International Eurasian Academy of Sciences, Fellow of the Royal Society of Edinburgh, Honorary Doctor of University of Glasgow and Hong Kong Baptist University. From 2014-2017, Prof. Rao served as the President of International Union for Pure and Applied Biophysics (IUPAB). From 2006-2017, he served as the Chairman of Biophysics Society of China
structures of the Herpes simplex virus type 2 B-capsid & C-capsid with capsid-vertex-specific component
Herpes simplex viruses (HSVs) cause human oral and genital ulcer diseases. Patients with HSV-2 have a higher risk of acquiring a human immunodeficiency virus infection. HSV-2 is a member of the α-herpesvirinae subfamily that together with the β- and γ-herpesvirinae subfamilies forms the Herpesviridae family. Structurally and genetically, human herpesviruses are amongst the largest and most complex of viruses. Using an optimized reconstruction strategy, we report the structures of HSV-2 B-capsid at 3.1 Å resolutions and C-capsid at 3.75 Å resolution which includes, 28,138 residues in the asymmetric unit, belonging to 46 different conformers of 4 capsid proteins (VP5, VP23, VP19C, VP26) making up 4 types of capsomers (C-Hex, E-Hex, P-Hex, Pen) and triplexes. Acting as core organizers, VP5s exhibit striking differences in configuration and mode of assembly to form extensive intermolecular networks, involving VP26s and triplexes via covalent (25 disulfide bonds per asymmetric unit) and non-covalent interactions, that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to the assembly of a massive quasi- symmetric shell, exemplifying the structural and functional complexity of HSV. We also present atomic models of multiple conformers for the C-capsid proteins (VP5, VP23, VP19C and VP26) and CVSC. Comparison of the HSV-2 homologues yields information about structural similarities and differences between the three herpesviruses sub-families and we identify α-herpesvirus-specific structural features. The hetero-pentameric CVSC, consisting of a UL17 monomer, a UL25 dimer and a UL36 dimer, is bound tightly by a five-helix bundle that forms extensive networks of subunit contacts with surrounding capsid proteins, which reinforce capsid stability. The portal structures of HSV2 B-capsid and C-capsid also discussed
Free and open to the university community and the public.
Nieng Yan, Department of Molecular Biology