We will make a set of X-ray measurements to determine the effect of trans-membrane protein concentration on the thickness profile of cell membranes. Such information, surprisingly unknown to date, will help in establishing an underlying framework for comparison of native and potentially pathological cellular membrane processes, which are known to correlate with membrane thickness. OmpF trimeric porins from E. coil will be reconstituted at a series of concentrations in lipid vesicles comprised of single lipid-types of varying lengths. Bilayer thickness profiles as a function of protein concentration and protein/lipid hydrophobic length mismatch will be measured. Computer simulations will augment the experimentally averaged thickness profiles by providing detailed molecular-level information regarding the interactions between the proteins and lipids comprising the membrane systems. A set of molecular dynamics simulations will be performed on the OmpF porin in an explicit bilayer setting. The simulations will address detailed structural adaptations (changes in bilayer thickness) to changes in protein concentration and lipid chain length. The impact of protein-protein correlations on bilayer thickness will be determined.
| Kajander, Tommi; Sachs, Jonathan N; Goldman, Adrian et al. (2009) Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90: computational analysis and protein engineering. J Biol Chem 284:25364-74 |
| Sachs, Jonathan N; Engelman, Donald M (2006) Introduction to the membrane protein reviews: the interplay of structure, dynamics, and environment in membrane protein function. Annu Rev Biochem 75:707-12 |
| Chin, Chen-Ni; Sachs, Jonathan N; Engelman, Donald M (2005) Transmembrane homodimerization of receptor-like protein tyrosine phosphatases. FEBS Lett 579:3855-8 |
