Biophysical Society Thematic Meeting - October 13-15, 2015

Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling

Poster Abstracts

22-POS Board 22 The Membrane Binding of C-reactive Protein Depends on Conformational State Aml Alnaas, Carrie L. Moon, Mitchell Alton, Michelle Knowles . University of Denver, Denver, USA. C-reactive protein (CRP) is an immune system protein that serves to protect the body by binding to damaged membranes. CRP is actively involved with the clearance of apoptotic cells and oxidized LDL by binding to the phosphatidylcholine (PC) head group in a calcium dependent manner. How CRP recognizes only damaged membranes, as opposed to healthy PC-containing membranes, is an interesting question that we aim to address in our research. Previous work on CRP suggests that there are at least two conformational states and these have different physiological function. In our work, we tested the membrane binding capabilities of two conformers, pentameric CRP and monomeric CRP. Monomeric CRP (mCRP) binds strongly to curved membranes in an in vitro supported lipid bilayer that has sites of curvature. Pentameric CRP (pCRP) avoids these sites of curvature. Curved membranes were created using a nanoparticle-patterned, supported lipid bilayer. Fluorescent nanoparticles (diameter = 40-200 nm) were deposited and subsequently coated with lipids then imaged by confocal microscopy. The downstream function of CRP is to bind to proteins in the complement immune response, which ultimately leads to the removal of apoptotic cells and oxidized LDL. Our fluorescence anisotropy work demonstrates that mCRP readily binds C1q, a complement protein, but pCRP does not. When mCRP is present on regions of membrane curvature, it recruits C1q. This work demonstrates that mCRP can bind to curved membranes and recruit complement immune proteins without the presence of lipids that are often part of damaged membranes, such as oxidized lipids and lysoPC.

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