Biochemistry & Molecular Biology Journal Open Access

Protein aggregation and protein-membrane interactions of the matrix (MA) domain of HIV-1 Gag protein

10^th Edition of International Conference on Structural Biology

March 15-16 2018 Barcelona, Spain

Viviana Monje-Galvan and Gregory Voth

The University of Chicago, USA

Scientific Tracks Abstracts: Biochem Mol biol J

Abstract:

Binding and aggregation of the HIV-1 Gag protein to the plasma membrane (PM) enables budding and release of immature virions, which further enables the propagation of viral infection. The matrix (MA) domain of the Gag protein is a 131-aminoacid sequence responsible for targeting the membrane. The MA domain seems to favor electrostatic interactions at the membrane surface in places where PIP2 lipids are more abundant. The myristate group (Myr), a fatty acid covalently attached to the N-terminus of the protein, serves as an anchor once initial binding occurs. The mechanism of Myr release from its binding pocket and its insertion into the membrane is still unclear. NMR studies suggest that MA trimerization facilitates Myr exposure from its sequestered conformation, leading to Myr anchoring. Using molecular dynamics and enhanced sampling techniques, such as metadynamics, we examined MA-membrane interactions with model membranes for the PM as well as MAMA interaction and trimerization. We looked at the effect of lipid composition, specifically the presence of PIP2 and cholesterol, on MA binding events and whether membrane-binding promotes lipid reorganization and raft formation. We present the protein conformational changes that take place during Myr exposure, MA-membrane binding, and MA trimerization. Computational resources for this work were available through XSEDE (Stampede2 and Bridges) and the Anton2 machine from the Pittsburgh Supercomputing Center.

Biography :

Viviana Monje-Galvan completed her PhD from the University of Maryland-College Park, USA. She is currently a Postdoctoral Scholar at the Voth Lab in the Chemistry Department at the University of Chicago. She has 10 publications, three as first author, and four more under preparation. She contributed with over 10 posters and oral presentations at multiple conferences and symposia since 2013, both in the USA as well as abroad. She has also presented her work as Invited Speaker at the “Universidad Mayor de San Andres” in seminar series prepared by the Departments of Physics and Chemical Engineering and the IBTEN (the national regulatory institution of nuclear energy in Bolivia).

Email:vmonje@uchicago.edu