Membrane Composition Modulates Vp54 Binding: A Combined Experimental and Computational Study

Area of Science:

• Biophysics
• Molecular Biology
• Computational Biology

Background:

• Peripheral membrane protein recruitment is regulated by lipid composition and local electrostatic conditions.
• Understanding protein-membrane interactions is key to cellular processes and disease mechanisms.

Purpose of the Study:

• To investigate the molecular basis of Vp54 viral matrix protein's selective binding to lipid bilayers.
• To elucidate the role of membrane lipid composition and electrostatic microenvironments in Vp54 recruitment.

Main Methods:

• Experimental observation of Vp54 binding to liposomes with varying lipid compositions.
• Computational analyses including helical wheel projection, electrostatic potential calculations, and field line/force simulations.

Main Results:

• Vp54 exhibits preferential binding to anionic lipids (phosphatidylglycerol, phosphatidylserine) in a curvature-dependent manner.
• Vp54 possesses a membrane-proximal amphipathic α-helical structure with a positively charged interface.
• Anionic lipid presence and clustering significantly enhance electrostatic attraction between Vp54 and the membrane.

Conclusions:

• Membrane lipid composition and organization critically modulate Vp54 recruitment through electrostatic complementarity.
• Findings highlight the importance of membrane heterogeneity in peripheral protein targeting.
• Provides a framework for understanding broader classes of membrane-binding proteins.