STRUCTURAL STUDIES OF VIRUSES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We study the structure of viruses and their components. We are interested in the assembly pathways and how viruses recognize, enter and infect their host. We make extensive use of electron microscopy to study viruses, or fragments of viruses, that cannot be crystallized. The relatively low resolution maps can be augmented by crystallographic studies of the protein components. 1. Flaviviruses: Structure of West Nile virus (Mukhopadhyay et al 2003, Science 302). Small crystals are available that diffract currently to about 20A resolution. Structure of components of flaviviruses such as E protein (Zhang et al. 2004, Structure 12) and capsid protein alone or in complex with potential drugs; viral enzymes. e.g. polymerase, Fab structures in complex with E. 2. Alphaviruses: Structures of the enveloped Ross River Virus and Sindbis virus (Zhang et al 2002, J.Virol 76). Crystals are available for Sindbis and small crystals of unknown diffraction quality for Ross River. Structure of components of alphaviruses such as E1 and E2 protein, capsid protein alone or in complex with drugs. 3. Parvoviridae: Capsid structures of several parvoviruses (Simpson et al 2002, JMB 315;Kaufmann et al. 2004, PNAS 101). Crystals are available for IHHNV, a shrimp pathogen. Attempts are being made to crystallize the PLA2 unique region of the capsid protein of PPV and B19. Crystals are available for Fab fragments of neutralizing antibodies. 4. Picornaviruses: Structure of ligands such as polio virus receptor, DAF and ICAM-1 (Zhang et al 2004, J Virol 78; Xiao et al 2005, Structure 13). 5. Pestiviruses: methyl transferase, polymerase (Choi et al 2002, PNAS 101) 6. Structural components of T4 phage: We have solved about 12 out of about 40 proteins so far (e.g. Fokine et al. 2005, PNAS 102). 7. Structural components of other phages: phiX174 (Bernal et al. 2004, JMB 337), phiKZ (Fokine et al. 2005, JMB 352), phi29 (Morais et al. 2005, Mol.Cell 18). Other projects, but no space