Myr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1

Yue Zhang, Olivier Soubias, Shashank Pant, Frank Heinrich, Alexander Vogel, Jess Li, Yifei Li, Luke A. Clifton, Sebastian Daum, Kirsten Bacia, Daniel Huster, Paul A. Randazzo, Mathias Lösche, Emad Tajkhorshid, R. Andrew Byrd

Research output: Contribution to journalArticlepeer-review


ADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics. Defining the dynamic conformational landscape of Arf1 in its active form, when bound to the membrane, is of high functional relevance and key to understanding how Arf1 can alter diverse cellular processes. Through concerted application of nuclear magnetic resonance (NMR), neutron reflectometry (NR) and molecular dynamics (MD) simulations, we show that, while Arf1 is anchored to the membrane through its N-terminal myristoylated amphipathic helix, the G domain explores a large conformational space, existing in a dynamic equilibrium between membrane-associated and membrane-distal conformations. These configurational dynamics expose different interfaces for interaction with effectors. Interaction with the Pleckstrin homology domain of ASAP1, an Arf-GTPase activating protein (ArfGAP), restricts motions of the G domain to lock it in what seems to be a conformation exposing functionally relevant regions.

Original languageEnglish (US)
Article number7570
JournalNature communications
Issue number1
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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