Coarse-grained simulations of adeno-associated virus and its receptor reveal influences on membrane lipid organization and curvature
Author(s)
Pipatpadungsin, Nichakorn
Chao, Kin
Rouse, Sarah L
Type
Journal Article
Abstract
Adeno-associated virus (AAV) is a well-known gene delivery tool with a wide range of applications, including as a vector for gene therapies. However, the molecular mechanism of its cell entry remains unknown. Here, we performed coarse-grained molecular dynamics simulations of the AAV serotype 2 (AAV2) capsid and the universal AAV receptor (AAVR) in a model plasma membrane environment. Our simulations show that binding of the AAV2 capsid to the membrane induces membrane curvature, along with the recruitment and clustering of GM3 lipids around the AAV2 capsid. We also found that the AAVR binds to the AAV2 capsid at the VR-I loops using its PKD2 and PKD3 domains, whose binding poses differs from previous structural studies. These first molecular-level insights into AAV2 membrane interactions suggest a complex process during the initial phase of AAV2 capsid internalization.
Date Issued
2024-10-17
Date Acceptance
2024-09-17
Citation
Journal of Physical Chemistry B, 2024, 128 (41), pp.10139-10153
ISSN
1520-6106
Publisher
American Chemical Society
Start Page
10139
End Page
10153
Journal / Book Title
Journal of Physical Chemistry B
Volume
128
Issue
41
Copyright Statement
© 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39356546
Subjects
Chemistry
Chemistry, Physical
CORECEPTOR
GROWTH-FACTOR RECEPTOR
LAMININ RECEPTOR
Physical Sciences
Science & Technology
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-10-02