We propose to determine the structure of HIV-1 VLPs halted at selected stages throughout maturation by cryo-electron tomography. This method will enable us to determine (1) the morphological changes the virus undergoes during maturation, (2) the structure of immature and mature HIV-1 VLPs with the Envelope protein (Env) expressed and how it is arranged in the matrix (MA) layer, and (3) the positions of other viral components within the particles. To achieve these aims, in collaboration with researchers at the University of Utah, we plan to (1) purify HIV-1 mutants halted at several 'developmental' stages, (2) image the HIV-1 mutants by cryo-electron tomography and calculate the structures through computational methods, and (3) determine the structural variability present in the specific viral proteins during maturation. Our studies will provide the highest resolution structures of whole, intact frozen-hydrated HIV-1 VLPs from which other researchers may determine the placement of other proteins and data from which new therapies may be designed to combat or eradicate HIV-1 infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
3F32GM075543-02S1
Application #
7347407
Study Section
AIDS Molecular and Cellular Biology Study Section (AMCB)
Program Officer
Flicker, Paula F
Project Start
2005-08-01
Project End
2007-07-31
Budget Start
2007-02-01
Budget End
2007-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$25,214
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Wright, Elizabeth R; Schooler, Jordan B; Ding, H Jane et al. (2007) Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J 26:2218-26