Understanding the role of membrane environment on membrane protein association and function

West Virginia University Research Corporation, Morgantown WV

Investigators

Abstract

Membrane proteins act as the gatekeepers of the cell, playing an intimate role in most biological functions. A detailed molecular description of how the membrane environment modulates association of membrane proteins will provide fundamental insights into biological processes that are linked to fields such as biomedicine, pharmaceuticals, and solar energy harvesting. Computational modeling approaches will be utilized to determine the effect of the cellular membrane on the association of membrane proteins. The advantage of computational modeling is that it can characterize the dynamics of association and dissociation of membrane proteins. The membrane protein to be studied is proteorhodopsin (PR), a protein common to microbial life in marine ecosystems. PR is a critical to survival of these microbes and their role in the carbon cycle may directly affect the ability of the ocean to accommodate fluctuations in the atmospheric environment. This project aims to model the effects of changing cell membrane composition on the function of PR and its association into multi-component complexes. Results will aid the biophysics community in their understanding of the relationship between cell membrane environment and protein function. In addition to training graduate and undergraduate students, the proposed research will involve professors and students from primarily undergraduate institutions in West Virginia. These students are from Appalachia, a traditionally underrepresented region in STEM fields. Thus, this project will develop long-term relationships for increasing student involvement in scientific research and encourage them to pursue careers in STEM fields. The specific objectives of this project are the characterization of the structure-function relationship of proton pumping in proteorhodopsin, the identification of key monomer-monomer interactions during oligomerization of this protein, and, determination of the relationship between membrane environment and oligomerization. Several molecular dynamics (MD) simulation approaches will be used to pursue each objective. Determination of conformational changes in PR activation will elucidate how proton pumping occurs. Characterization of the relationship between membrane composition and oligomerization will reconcile conflicting hypotheses on oligomerization of PR in native-like and non-native membrane environments. This will also contribute to knowledge of membrane protein interactions in systems such as bacterial inner membranes. Insights obtained will provide a general framework for interpretation and design of detergent-membrane protein experiments, since detergent solubilization is the de facto method for these studies.