Distinct EH domains of the endocytic TPLATE complex confer lipid and protein binding.Distinct EH domains of the endocytic TPLATE complex confer lipid and protein binding

Klaas Yperman, Anna C. Papageorgiou, Romain Merceron, Steven De Munck, Yehudi Bloch, Dominique Eeckhout, Pieter Tack, Thomas Evangelidis, Jelle Van Leene, Laszlo Vincze, Peter Vandenabeele, Martin Potocký, Geert De Jaeger, Savvas N. Savvides, Konstantinos Tripsianes, Roman Pleskot, Daniel Van Damme

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Received Date: 19th May 20

Clathrin-mediated endocytosis (CME) is the gatekeeper of the plasma membrane. In contrast to animals and yeasts, CME in plants depends on the TPLATE complex (TPC), an evolutionary ancient adaptor complex. The mechanistic contribution of the individual TPC subunits to plant CME remains however elusive. In this study, we used a multidisciplinary approach to elucidate the structural and functional roles of the evolutionary conserved N-terminal Eps15 homology (EH) domains of the TPC subunit AtEH1/Pan1. By integrating high-resolution structural information obtained by X-ray crystallography and NMR spectroscopy with all-atom molecular dynamics simulations, we provide structural insight into the function of both EH domains. Whereas one EH domain binds negatively charged PI(4,5)P2 lipids, unbiased peptidome profiling by mass-spectrometry revealed that the other EH domain interacts with the double N-terminal NPF motif of a novel TPC interactor, the integral membrane protein Secretory Carrier Membrane Protein 5 (SCAMP5). Furthermore, we show that AtEH/Pan1 proteins control the internalization of SCAMP5 via this double NPF peptide interaction motif. Collectively, our structural and functional studies reveal distinct but complementary roles of the EH domains of AtEH/Pan1 have in plant CME and connect the internalization of SCAMP5 to the TPLATE complex.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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