Abstract

The goal of the proposed research is to determine the three dimensional structure of poliomyelitis virus at high resolution by X-ray crystallographic methods. Poliovirus is a member of the enterovirus group of the picornavirus family. The picornaviruses, and poliovirus in particular, have been well characterized biologically. Poliovirus thus serves as a excellent model system for understanding the structural basis for several important properties of animal viruses including: assembly, antigenic properties, mechanism of neutralization by antibodies, recognition by host cell receptors, and the mechanism of penetration and entry into susceptible cells. Crystals have been obtained from both the Sabin (attentuated) and the Mahoney (virulent) strains of the type I serotype of poliovirus. To date, the crystals of the Mahoney strain have proved more suitable for X-ray crystallographic studies. The crystals of the Mahoney strain belong to the space group P21212 with unit cell constants a=324 A, b=359 A, c=381 A and diffract to at least 2.2 A resolution. The structure determination will use methods devised and tested for previous successful crystallographic studies of plant viruses.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020566-02
Application #
3130297
Study Section
Biophysics and Biophysical Chemistry B Study Section (BBCB)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Zhao, Zhao; Zhang, Meng; Hogle, James M et al. (2018) DNA-Corralled Nanodiscs for the Structural and Functional Characterization of Membrane Proteins and Viral Entry. J Am Chem Soc 140:10639-10643
Nasr, Mahmoud L; Baptista, Diego; Strauss, Mike et al. (2017) Covalently circularized nanodiscs for studying membrane proteins and viral entry. Nat Methods 14:49-52
Groppelli, Elisabetta; Levy, Hazel C; Sun, Eileen et al. (2017) Picornavirus RNA is protected from cleavage by ribonuclease during virion uncoating and transfer across cellular and model membranes. PLoS Pathog 13:e1006197
Strauss, Mike; Schotte, Lise; Karunatilaka, Krishanthi S et al. (2017) Cryo-electron Microscopy Structures of Expanded Poliovirus with VHHs Sample the Conformational Repertoire of the Expanded State. J Virol 91:
Strauss, Mike; Schotte, Lise; Thys, Bert et al. (2016) Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site. J Virol 90:3496-505
Schotte, Lise; Thys, Bert; Strauss, Mike et al. (2015) Characterization of Poliovirus Neutralization Escape Mutants of Single-Domain Antibody Fragments (VHHs). Antimicrob Agents Chemother 59:4695-706
Strauss, Mike; Filman, David J; Belnap, David M et al. (2015) Nectin-like interactions between poliovirus and its receptor trigger conformational changes associated with cell entry. J Virol 89:4143-57
Panjwani, Anusha; Strauss, Mike; Gold, Sarah et al. (2014) Capsid protein VP4 of human rhinovirus induces membrane permeability by the formation of a size-selective multimeric pore. PLoS Pathog 10:e1004294
Ma, Hsin-Chieh; Liu, Ying; Wang, Chunling et al. (2014) An interaction between glutathione and the capsid is required for the morphogenesis of C-cluster enteroviruses. PLoS Pathog 10:e1004052
Moustafa, Ibrahim M; Korboukh, Victoria K; Arnold, Jamie J et al. (2014) Structural dynamics as a contributor to error-prone replication by an RNA-dependent RNA polymerase. J Biol Chem 289:36229-48

Showing the most recent 10 out of 33 publications