Membrane surface recognition by the ASAP1 PH domain and consequences for interactions with the small GTPase Arf1

Olivier Soubias, Shashank Pant, Frank Heinrich, Yue Zhang, Neeladri Sekhar Roy, Jess Li, Xiaoying Jian, Marielle E. Yohe, Paul A. Randazzo, Mathias Lösche, Emad Tajkhorshid, R. Andrew Byrd

Research output: Contribution to journalArticlepeer-review

Abstract

Adenosine diphosphate-ribosylation factor (Arf) guanosine triphosphatase-activating proteins (GAPs) are enzymes that need to bind to membranes to catalyze the hydrolysis of guanosine triphosphate (GTP) bound to the small GTP-binding protein Arf. Binding of the pleckstrin homology (PH) domain of the ArfGAP With SH3 domain, ankyrin repeat and PH domain 1 (ASAP1) to membranes containing phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is key for maximum GTP hydrolysis but not fully understood. By combining nuclear magnetic resonance, neutron reflectometry, and molecular dynamics simulation, we show that binding of multiple PI(4,5)P2 molecules to the ASAP1 PH domain (i) triggers a functionally relevant allosteric conformational switch and (ii) maintains the PH domain in a well-defined orientation, allowing critical contacts with an Arf1 mimic to occur. Our model provides a framework to understand how binding of the ASAP1 PH domain to PI(4,5)P2 at the membrane may play a role in the regulation of ASAP1.

Original languageEnglish (US)
Article numbereabd1882
JournalScience Advances
Volume6
Issue number40
DOIs
StatePublished - Sep 30 2020

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Membrane surface recognition by the ASAP1 PH domain and consequences for interactions with the small GTPase Arf1'. Together they form a unique fingerprint.

Cite this