Coarse-grained simulations suggest potential competing roles of phosphoinositides and amphipathic helix structures in membrane curvature sensing of the AP180 N-terminal homology domain

Title: Coarse-grained simulations suggest potential competing roles of phosphoinositides and amphipathic helix structures in membrane curvature sensing of the AP180 N-terminal homology domain
Authors: Belessiotis-Richards, A
Larsen, AH
Higgins, SG
Stevens, MM
Alexander-Katz, A
Item Type: Journal Article
Abstract: The generation and sensing of membrane curvature by proteins has become of increasing interest to researchers with multiple mechanisms, from hydrophobic insertion to protein crowding, being identified. However, the role of charged lipids in the membrane curvature-sensing process is still far from understood. Many proteins involved in endocytosis bind phosphatidylinositol 4,5-bisphosphate (PIP2) lipids, allowing these proteins to accumulate at regions of local curvature. Here, using coarse-grained molecular dynamics simulations, we study the curvature-sensing behavior of the ANTH domain, a protein crucial for endocytosis. We selected three ANTH crystal structures containing either an intact, split, or truncated terminal amphipathic helix. On neutral membranes, the ANTH domain has innate curvature-sensing ability. In the presence of PIP2, however, only the domain with an intact helix senses curvature. Our work sheds light on the role of PIP2 and its modulation of membrane curvature sensing by proteins.
Issue Date: 21-Apr-2022
Date of Acceptance: 8-Apr-2022
URI: http://hdl.handle.net/10044/1/97363
DOI: 10.1021/acs.jpcb.2c00239
ISSN: 1520-5207
Publisher: American Chemical Society
Start Page: 2789
End Page: 2797
Journal / Book Title: The Journal of Physical Chemistry B: Biophysical Chemistry, Biomaterials, Liquids, and Soft Matter
Volume: 126
Issue: 15
Copyright Statement: © 2022 The Authors. Published by American Chemical Society
Sponsor/Funder: Engineering and Physical Sciences Research Council
Funder's Grant Number: EP/L015277/1
Keywords: Science & Technology
Physical Sciences
Chemistry, Physical
Chemistry
VESICLE SIZE
COATED PITS
CLATHRIN
PROTEINS
ENDOCYTOSIS
EFFICIENT
INSERTION
FISSION
ACTIN
Cell Membrane
Endocytosis
Molecular Dynamics Simulation
Phosphatidylinositols
Proteins
Cell Membrane
Phosphatidylinositols
Proteins
Endocytosis
Molecular Dynamics Simulation
Science & Technology
Physical Sciences
Chemistry, Physical
Chemistry
VESICLE SIZE
COATED PITS
CLATHRIN
PROTEINS
ENDOCYTOSIS
EFFICIENT
INSERTION
FISSION
ACTIN
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status: Published
Appears in Collections:Materials



This item is licensed under a Creative Commons License Creative Commons