University of Connecticut

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CCAM Seminar Series - Margaret Johnson

Thursday, May 5, 2016
4:00pm – 5:00pm

UConn Health
CCAM CGSB, Conference Room, R1673, 400 Farmington Ave

CCAM Seminar Series Speaker - Margaret Johnson, Assistant Professor, Department of Biophysics, Johns Hopkins University Title: "Mechanisms of protein assembly at the membrane: Insights from theory and reaction-diffusion simulation"

Abstract: Membrane targeting and assembly of proteins is required for vesicle trafficking and receptor mediated signaling, but the extent to which the proteins recruited to these events may have evolved to exploit the 2D surface for assembly, versus pre-assembling in solution, is not known. Through theory and simulation, we have found that for the great majority of membrane targeting proteins, surface recruitment dramatically enhances their effective binding strength and subsequent complex formation. The membrane both reduces the search space and induces a cooperative binding effect for stabilizing complexes with multiple lipid binding sites. We show that the magnitude of enhancement has a simple functional form that applies whenever lipid recruiter concentrations are sufficiently high, and surprisingly, is independent of the protein binding strength. We propose that membrane localization works as a mechanism that ensures assembly only at specific times (after recruitment to surfaces) but does not precisely regulate the proteins involved, since they benefit equally from surface restriction. This robust but nonspecific strategy is employed by proteins involved in vesicle trafficking , but proteins participating in signaling likely require more precise regulatory control. These results were obtained using novel algorithms derived in our group for simulating reactions between diffusing proteins at single-particle resolution. We have recently developed new approaches to capture rigid body motion and assembly in the framework of reaction-diffusion models. In addition to the work discussed here, these simulation tools will be useful in establishing why and how assembly occurs in a wide range of processes such as cytoskeletal assembly and transcription initiation.

Host: Dr. Ion Moraru


Tiffany Gough,

Center for Cell Analysis and Modeling (primary), School of Medicine, UConn Health Dept of Medicine

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