Biophysical Society Thematic Meeting | Tutzing 2026

Single-Molecule FRET: The Next 30 Years

Poster Abstracts

20-POS Board 10 DECODING AP180 BY INTEGRATIVE SPECTROSCOPY - MOLECULAR MECHANISMS OF CLATHRIN COAT ASSEMBLY Philipp A Gansen 1 ; Kathrin Motzny 1 ; Johannes Broichhagen 1 ; Sigrid Milles 1 ; 1 Leibniz-Forschungsinstitut fuer Molekulare Pharmakologie, Berlin, Germany Clathrin-mediated endocytosis (CME) relies on a highly dynamic network of protein interactions, many of which are mediated by intrinsically disordered adaptor proteins. The neuronal adaptor AP180 and its ubiquitous homologue CALM are central regulators of the fundamental clathrin coat assembly, yet the molecular mechanisms by which their long intrinsically disordered regions control this process remain poorly understood. While previous studies have emphasized short linear motifs that bind the clathrin heavy chain terminal domain, recent Nuclear Magnetic Resonance (NMR) data suggest a more complex interaction landscape that might serve as the origin of successful and efficient clathrin assembly. I now employ an integrative spectroscopy approach combining solution NMR, single-molecule FRET and the development of novel hybrid labels to dissect the many stages of this dynamic process. In particular, we utilize a large toolbox of NMR experiments, single-molecule fluorescence measurements and in silico modeling to cover a plethora of time and distance regimes of adaptor-clathrin interactions. This will enable us to trace how intrinsic disorder, transient structure, and multivalency govern and catalyse clathrin assembly.

110