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BP: Fachverband Biologische Physik
BP 65: Membranes and Vesicles II
BP 65.4: Talk
Thursday, March 10, 2016, 16:00–16:15, H43
An entropic attraction mediates vesicle tethering in early endosomes — •Marcus Jahnel1, 2, David Murray1, Marino Zerial1, and Stephan Grill1, 2 — 1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany — 2Biotechnology Center, TU Dresden, Dresden, Germany
Vesicle tethering is mediated by long, rather rigid coiled-coil membrane proteins that can bind Rab GTPases at their free end. Yet it is still unclear how these large fibrous proteins help to decrease the initial separation between two membranes for downstream docking and fusion. Which mechanism brings the two ends together?
Here, we address this question with a minimal tethering system consisting of the small GTPase Rab5 and the coiled-coil tethering protein early endosome antigen 1 (EEA1). Importantly, we show through a combination of high-resolution optical tweezer and EM experiments that EEA1 undergoes a global conformational change upon binding to Rab5 in the presence of GTP.
In the unbound (free) state EEA1 is rather rigid with a persistence length larger than its contour length of around 220 nm. However, in the bound state, the EEA1 dimer adopts a more flexible configuration with a persistence length of < 30 nm. This sudden, over 10-fold reduction in persistence length upon binding gives rise to an elegant physical mechanism for vesicle capture and tethering: an entropic collapse force --- the result of an extended rigid structure suddenly becoming more flexible --- pulls the membranes together to potentially initiate docking and fusion.