Tuesday, December 5, 2017
1:00 p.m. Room 202 MRB
Professor Blake Mertz
Assistant Professor, C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia
Understanding the role of hydration in activation of a membrane protein
Proteorhodopsin (PR) is a membrane protein that functions as a light-driven proton pump, harvesting photons to generate a proton gradient across the inner membrane of marine bacteria to facilitate ATP synthesis. Since its initial discovery in 2000, PR has been found in soil-bound bacteria, fungi, viruses, and even eukaryotes, indicating that it may be involved in a multitude of essential components of the global ecosystem. Although we have a general idea of how PR functions, the specifics of the proton-pumping mechanism remain poorly understood. Molecular dynamics (MD) simulations are able to characterize dynamical fluctuations of molecular interactions on the atomistic scale, providing an invaluable tool with which to investigate biophysical phenomena. We have carried out MD simulations to identify the effect of protonation of a single amino acid residue on the inactive and initial activated states of PR. This glutamic acid residue (E108) is responsible for helping shuttle excess protons from the cytoplasm to the binding pocket in the interior of PR. The protonation state of the corresponding residue in similar proteins has been shown to act as a latch for conformational release of the cytoplasmic side of the protein, allowing it to quickly open and close to bulk water. Our simulations show that in PR, E108 has a slightly different mechanism, acting as a gate to restrict influx of bulk waters into the interior of the protein. Interestingly we observe that sidechain fluctuations of E108 are coupled o distal regions of PR, capturing long-range crosstalk that may play a vital role in the proton-pumping mechanism. This atomistic picture provides worthwhile insights into the function of PR and a rich context for extended interpretations of spectroscopic studies.