Coarse-grained simulations suggest phosphoinositides and amphipathic helix structure play opposing roles in membrane curvature sensing of the AP180 N-terminal homology domain
File(s)
Published version
Author(s)
Belessiotis-Richards, A
Larsen, AH
Higgins, SG
Alexander-Katz, A
Stevens, Molly
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.
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.
Date Issued
2022-04-21
Date Acceptance
2022-03-24
Citation
The Journal of Physical Chemistry B: Biophysical Chemistry, Biomaterials, Liquids, and Soft Matter, 2022, 126 (15), pp.2789-2797
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. This article is open access under a CC-BY 4.0 License (https://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Engineering and Physical Sciences Research Council
Commission of the European Communities
Wellcome Trust
Cancer Research UK
Grant Number
EP/L015277/1
ERC-2013-CoG-616417
098411/Z/12/Z
30035
Subjects
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status
Published
Date Publish Online
2022-04-08