STRUCTURAL STUDIES OF VIRUSES

这个子项目是众多研究子项目之一

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 viral assembly pathways, viral interaction with the host and entry mechanisms. 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 Science 2003). Crystals are available that diffract currently to about 16A resolution. Structure of components of flaviviruses such as E protein (Zhang et al. 2004, Structure 12) and capsid protein alone or in complex with precursor membrane protein; viral enzymes (Zhang et al Structure 2007) , Fab structures in complex with E (Kaufmann et al PNAS 2006). 2. Alphaviruses:Structure of components of alphaviruses such as E1 and E2 protein, capsid protein alone and in complex with drugs. 3. Parvoviridae:Capsid structures of several parvoviruses (Simpson et al JMB 2002; Kaufmann et al. PNAS 2004). Crystals are available for a shrimp virus and a silk worm viruses, a human parvovirus and a mouse virus. 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 J Virol 2004; Xiao et al 2005). 5. Structural components of T4 phage:We have solved about 15 out of about 40 proteins so far (e.g. Fokine et al. 2005; Sun Mol. Cell 2007). We have crystals of T4 sheath protein fragments, other tail proteins, the hoc and soc head proteins and the terminase enzymes. 6. Structural components of other phages:The H pilot protein of phiX174 (Bernal et al. JMB 2004),the lysozyme of phiKZ (Fokine et al.JMB 2005), gp13, gp9 cell lysing enzymes of phi29 (Morais et al. Moll Cell 2005). 7.Mimivirus structural proteins more, but no space