TY - JOUR
T1 - Myr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1
AU - Zhang, Yue
AU - Soubias, Olivier
AU - Pant, Shashank
AU - Heinrich, Frank
AU - Vogel, Alexander
AU - Li, Jess
AU - Li, Yifei
AU - Clifton, Luke A.
AU - Daum, Sebastian
AU - Bacia, Kirsten
AU - Huster, Daniel
AU - Randazzo, Paul A.
AU - Lösche, Mathias
AU - Tajkhorshid, Emad
AU - Byrd, R. Andrew
N1 - The authors acknowledge the use of the Biophysics Resource, Center for Structural Biology, NCI, and the assistance of Dr. Sergey Tarasov and Ms. Marzena Dyba. The research was supported by the Intramural Research Program of the National Cancer Institute (Projects ZIA BC 011419, ZIA BC 011131, and ZIA BC 011132 supported O.S., Y.Z., J.L., and R.A.B.; Project BC007365 supported P.A.R.). The computational component of this study was supported by the NIH under Awards P41-GM104601 (to E.T.) and R01-GM123455 (to E.T.). We also acknowledge computing resources provided by Blue Waters at the National Center for Supercomputing Applications and Extreme Science and Engineering Discovery Environment (Award MCA06N060 to E.T.). S.P. would like to thank the Beckman Institute Graduate Fellowship for funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. F.H. and M.L. were supported by the U.S. Department of Commerce, Award 70NANB17H299. The research was performed, in part, at the National Institute of Standards and Technology (NIST) Center for Nanoscale Science and Technology. Certain commercial materials, equipment, and instruments are identified in this work to describe the experimental procedure as completely as possible. In no case does such an identification imply a recommendation or endorsement by NIST, nor does it imply that the materials, equipment, or instrument identified is necessarily the best available for the purpose.
The authors acknowledge the use of the Biophysics Resource, Center for Structural Biology, NCI, and the assistance of Dr. Sergey Tarasov and Ms. Marzena Dyba. The research was supported by the Intramural Research Program of the National Cancer Institute (Projects ZIA BC 011419, ZIA BC 011131, and ZIA BC 011132 supported O.S., Y.Z., J.L., and R.A.B.; Project BC007365 supported P.A.R.). The computational component of this study was supported by the NIH under Awards P41-GM104601 (to E.T.) and R01-GM123455 (to E.T.). We also acknowledge computing resources provided by Blue Waters at the National Center for Supercomputing Applications and Extreme Science and Engineering Discovery Environment (Award MCA06N060 to E.T.). S.P. would like to thank the Beckman Institute Graduate Fellowship for funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. F.H. and M.L. were supported by the U.S. Department of Commerce, Award 70NANB17H299. The research was performed, in part, at the National Institute of Standards and Technology (NIST) Center for Nanoscale Science and Technology. Certain commercial materials, equipment, and instruments are identified in this work to describe the experimental procedure as completely as possible. In no case does such an identification imply a recommendation or endorsement by NIST, nor does it imply that the materials, equipment, or instrument identified is necessarily the best available for the purpose.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-43008-5
DO - 10.1038/s41467-023-43008-5
M3 - Article
C2 - 37989735
AN - SCOPUS:85177444625
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7570
ER -