Structural Studies of HIV-1 gp41 MPER and HR-2 Membrane Associated Trimers
EMSL Project ID
47468
Abstract
HIV-1 viral-host cell fusion is mediated by the envelope associated gp41 and gp120 protein trimers. The membrane proximal external region (MPER) of gp41 contains the epitopes for the broadly neutralizing HIV-1 antibodies 2F5 and 4E10. We have developed new trimeric gp41 constructs that include the MPER domain associated with phospholipid membranes. Our proposed studies address the Biological Interactions and Dynamics science theme by determining the atomic resolution structures of these constructs and characterizing their interactions with the phospholipid membrane. To accomplish this work, we are requesting time on the 600, 850, and 900 MHz instruments for solid state protein NMR, access to the Chinook supercomputer for CS-ROSETTA calculations, time on the EMSL CRYO-EM system, and use of EMSL wet-lab resources for sample preparation. The structures determined by this research effort will be deposited in the protein databank and published. This study will reveal how the interactions between membrane proximal domains and membranes can influence protein function. Additionally, studies of the neutralizing antibodies in complex with these constructs will lead to a better understanding of how the membrane surface can assist the antibody/epitope binding event.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2012-10-01
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members