Membrane curvature recognition by C-reactive protein using lipoprotein mimics

Area of Science:

• Biochemistry
• Immunology
• Materials Science

Background:

• C-reactive protein (CRP) is known to bind oxidized phosphatidylcholine (PC) lipids on cell membranes.
• The precise reasons for CRP's selective binding to oxidized membranes remain unclear.
• Understanding CRP binding is crucial for its role in inflammation and immune response.

Purpose of the Study:

• To investigate the role of membrane curvature in CRP binding to lipid membranes.
• To explore alternative factors beyond lipid oxidation that influence CRP's interaction with damaged membranes.
• To characterize the structural changes in CRP upon binding to specific lipid structures.

Main Methods:

• Utilized engineered lipoprotein particle (LPP) mimics with varying diameters to simulate membrane curvature.
• Assessed CRP binding affinity to LPP mimics of different sizes.
• Analyzed CRP structural changes (dissociation into monomers) and neo-epitope exposure using biophysical techniques.
• Investigated competitive binding between LPP mimics and oxidized low-density lipoproteins (oxLDLs).

Main Results:

• CRP demonstrated preferential binding to LPP mimics with smaller diameters (≤ 28 nm), indicating a role for membrane curvature.
• CRP binding to these mimics induced dissociation into monomeric CRP, exposing neo-epitopes recognized by C1q.
• Smaller LPP mimics competed with oxLDLs for CRP binding, suggesting shared PC epitopes.

Conclusions:

• Membrane curvature, in addition to PC oxidation, is a significant factor influencing CRP binding to damaged membranes.
• CRP's structural transformation upon binding to curved structures exposes new binding sites for complement activation.
• Engineered LPP mimics serve as valuable tools for dissecting the complex interactions of CRP with lipid environments.