Interaction Interface of Mason-Pfizer Monkey Virus Matrix and Envelope Proteins

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• Retroviral envelope glycoprotein (Env) mediates host cell recognition and infection initiation.
• Env recruitment into the viral membrane involves interaction with the Gag polyprotein precursor.
• For human immunodeficiency virus (HIV), this interaction occurs between Gag's matrix domain (MA) and Env's cytoplasmic tail (CT) at the plasma membrane.

Purpose of the Study:

• To investigate direct interaction between Mason-Pfizer monkey virus (M-PMV) MA and Env's CT.
• To determine the specific residues involved in the MA-CT interaction.
• To elucidate the structural basis of M-PMV Env-Gag interaction at the host cell membrane.

Main Methods:

• In vitro experiment mimicking in vivo conditions using a trimeric CT and MA protein.
• Pulldown assay to confirm direct MA-CT interaction.
• Nuclear magnetic resonance (NMR) spectroscopy and cross-linking followed by mass spectrometry to identify interacting residues.

Main Results:

• Direct interaction between M-PMV MA and CT was confirmed.
• NMR revealed CT C-terminus binding to MA C-terminal part.
• Cross-linking indicated proximity between CT N-terminus and MA N-terminus, facilitated by membrane localization.

Conclusions:

• M-PMV MA interacts with the C-terminal residues of the Env CT, unlike HIV-1.
• A model is proposed where CT monomers bind MA from neighboring trimers, stabilizing MA at the membrane.
• This interaction mechanism may differ between retroviral types based on CT length and influences virus assembly and uncoating.