Recognition between CD147 and cyclophilin A deciphered by accelerated molecular dynamics simulations.

Area of Science:

• Molecular biology
• Virology
• Immunology

Background:

• CD147 acts as an extracellular cyclophilin A (CypA) receptor, implicated in various diseases.
• CD147-CypA binding contributes to pathological processes in viral infections like HIV-1, SARS, and SARS-CoV-2.
• The precise mechanism of CD147-CypA cooperation in cytokine storm development and their binding profile remain unclear.

Purpose of the Study:

• To elucidate the binding mechanism and profile between CD147 and CypA.
• To investigate the role of specific CD147 residues in modulating CD147-CypA interactions.
• To understand the implications for inflammation and viral pathogenesis.

Main Methods:

• Preparation of three CD147-CypA binding models.
• Accelerated molecular dynamics simulations.
• Molecular mechanics generalized Born surface area (MM/GBSA) calculations and residue mutations (P180A-G181A, P211A).

Main Results:

• CypA exhibits the highest binding affinity to the CD147 ectodomain in model-0.
• Mutations P180A-G181A in CD147 significantly reduced binding affinity and weakened dynamic correlation, causing CypA displacement.
• Residue R201 of CD147 was identified as critical for CD147-CypA binding, requiring further experimental validation.

Conclusions:

• CD147-CypA binding occurs primarily within the groove of CD147, modulated by residues P180-G181.
• The P180-G181 interaction is more significant than P211 in modulating CD147-CypA binding.
• Findings enhance understanding of CD147-CypA recruitment in inflammation and viral infection.