Oct 6
Chemistry Department Seminar: Andrew Nieuwkoop, Rutgers
"Characterization of Kindlin-2 Binding to Lipid Bilayers Containing Phosphatidylinositol Phosphates"
The Nieuwkoop lab studies membranes and membrane binding using NMR. Kindlin-2 (K2) is a peripheral membrane protein regulated in part through its binding to membranes containing the signaling lipids phosphatidylinositol phosphates (PIPs). We seek to understand this regulation by investigating PIPs in model lipid bilayers and the PIP binding sites of K2 PIP binding domains, characterizing the effects of PIP binding on the structure and dynamics of K2. Guided by the results of all atom and coarse-grained molecular dynamics simulations, we use solution and solid-state NMR to investigate the binding sites of the F0 and PH PIP binding domains of K2. 1H detected solid-state NMR experiments at 100+ kHz MAS pair with solution NMR titrations with IP4 (a soluble PIP headgroup analog) and PIP liposomes as well as solid-state experiments on PIPs in lipid bilayers. 1H, 13C, 15N and 31P-detected experiments acquired at static, 15, and 40 kHz MAS are also used to fully characterize the PIPs in the lipid bilayer, under a variety of conditions. We seek to understand how each parameter affects the PIPs and how in turn the membrane, and PIPs in particular, interacts with K2.
*This seminar counts towards the chemistry major seminar attendance requirement.