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Bioengineering Seminar Series: Jeffrey Klauda
Friday, March 29, 2013
11:00 a.m.-12:00 p.m.
Room 1200, Jeong H. Kim Engineering Building
For More Information:
Professor Ian White
ianwhite@umd.edu
E. coli Plasma Membrane Modeling and Membrane-associated Transport Proteins
Jeffrey Klauda
Assistant Professor
Dept. of Chemical and Biomolecular Engineering
University of Maryland, College Park
Lipid membranes protect cells from unwanted compounds and proteins control the transport of substrates between and across cellular membranes. The composition of these membranes varies significantly between organisms and organelles within an organism, which ultimately plays an important role in membrane structure and interaction with membrane-associated proteins. Our studies on the cytoplasmic membrane of E. coli with its unique lipid containing a cyclopropane moiety on its chain demonstrate the importance of lipid diversity to membrane structure and rigidity. Our E. coli membrane model agrees with known hydrophobic thicknesses of transmembrane proteins and is thinner than existing simple models for the cytoplasmic membrane. With accurate model membranes, simulations on membrane-associated proteins can provide insight on how proteins transport substrate across the membrane or between membranes. Lactose permease (LacY) of E. coli is a model for secondary active transporters (SATs) but most SATs have crystal structures in a single state in the transport cycle. To study substrate transport mechanism, we have developed a simulation technique to enhance conformational sampling of SAT proteins. This method was successful in obtaining the unknown periplasmic-open state of LacY and our simulations agree with a multitude of experimental measurements (FRET, DEER, accessibility studies, etc.). With a crystal structure in a single conformational state, our method can probe other states in the substrate transport cycle. While SAT proteins span the lipid bilayer, peripheral membrane proteins transiently bind to membranes and are involved in membrane signaling and transport. Our multiple μs all-atom simulations of the peripheral membrane protein of yeast (Osh4) have clarified how this protein binds to membranes. Previous experimental mutation studies suggested that Osh4 contained 2-3 distinct membrane binding domains. However, our simulations on similar model membranes used in experiments demonstrate a single membrane binding region. Since the membrane binding region on Osh4 agrees with previous experiments, it appears that Osh4 has a single large membrane binding domain. Ultimately, our goal is to probe how Osh4 transports sterols and an important signaling lipid between organelles in yeast.
This Event is For: Graduate • Faculty • Post-Docs
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