Lecture 20: Dr. Osman Yogurtcu (Margaret Johnson Lab)

Membrane Recruitment Enables Weak Binding Endocytic Proteins to Form Stable Complexes Membrane targeting and assembly of proteins is required for vesicle trafficking and receptor mediated signaling, but it is not known to what extent the proteins recruited to these events may have evolved to exploit the 2D surface for assembly, versus pre-assembling in solution. We show that the phospholipid targeting proteins of clathrin-mediated endocytosis dramatically enhance their effective binding strength and subsequent complex formation to one another after surface recruitment in yeast and metazoans. For proteins such as clathrin that do not directly bind lipids, the enhancement is still achieved by using three distinct binding sites to stabilize the clathrin to peripheral membrane proteins on the surface. We derive simple formulas that quantify the degree of binding enhancement as a function of the protein and lipid concentrations, binding constants, and critically, the ratio of volume to membrane surface area. Our results thus apply to any cell type or geometries, including in vitro systems and the targeting of internal organelles from the cytoplasm. With a sufficient concentration of lipid recruiters, such as PIP2, we show that the effective binding strength is enhanced by orders of magnitude and becomes, surprisingly, independent of the protein-protein binding strength. We quantify how this effect varies for proteins involved in later stages of vesicle trafficking and cell division in yeast. Coupled with detailed spatially and structurally resolved simulations, we have further measured the effect of membrane recruitment on controlling the speed of assembly, and influences of crowding and diffusion on this process.

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Osman N. Yogurtcu began his career in science as an undergraduate at Koc University, Turkey using computational polymer models to study protein-drug interactions. He received his M.Sc. in computational science and engineering from the same institution. During his Ph.D. in the Mechanical Engineering Department at the Johns Hopkins University, his research focused on mechanical properties of biofilaments, such as actin, that have crucial importance on cell viability. After graduation, he joined Prof. Margaret Johnson's lab in Johns Hopkins biophysics department where they worked on computational modelling of receptor mediated endocytosis.