Understanding Periperal Membrane Protein Interactions | BPS Thematic Meeting

Understanding Peripheral Membrane Protein Interactions: Structure, Dynamics, Function and Therapy

Poster Abstracts

1-POS Board 1 EXPLORING FILOVIRUS MATRIX PROTEIN VP40-MEMBRANE INTERACTIONS Prem Chapagain 1 ; 1 Florida International University, Department of Physics & Biomolecular Sciences, Miami, Florida, USA Ebolavirus (EBOV), a member of the Filoviridae family, causes severe hemorrhagic fevers with high mortality rates. The EBOV matrix protein VP40 is multifunctional but primarily responsible for forming the viral envelope by binding to the inner leaflet of the host cell’s plasma membrane (PM). VP40 assembles into a matrix layer beneath the PM, giving the virus its characteristic cylindrical shape. This process begins with dimeric VP40 interacting with lipid head groups via basic residues in the C-terminal domain (CTD) and these VP40–membrane interactions are essential for virion formation and viral egress. Mutations at the membrane-binding interface, particularly in the CTD, can significantly alter VP40 assembly and affect virion morphology. impacting viral assembly and budding. Mutagenesis studies have shown that mutations in the CTD loop region that contacts the PM strongly influence VP40 matrix formation. To explore the dynamics of membrane association of VP40 dimers and their oligomerization at the membrane surface, we performed all-atom and coarse-grained molecular dynamics simulations using a dimer–dimer configuration involving the CTD–CTD interface. These simulations allowed us to identify key residue-lipid interactions that stabilize VP40 dimers at the membrane. Our findings suggest that the location of mutations on the CTD outer surface can alter membrane binding orientation and penetration depth. Additionally, direct interactions with PI(4,5)P ₂ enhance membrane insertion and stabilize VP40 by promoting interactions with residues that are otherwise rarely engaged.

41