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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.