Binding of the monomeric form of C-reactive protein to enzymatically-modified low-density lipoprotein: effects of phosphoethanolamine.
BACKGROUND
The 5 subunits of native pentameric C-reactive protein (CRP) are dissociated to generate the monomeric form of CRP (mCRP) in some in vitro conditions, both physiological and non-physiological, and also in vivo. Many bioactivities of mCRP generated by urea-treatment of CRP and of mCRP generated by mutating the primary structure of CRP have been reported. The bioactivities of mCRP generated by spontaneous dissociation of CRP are largely unexplored.


METHODS
We purified mCRP generated by spontaneous dissociation of CRP and investigated the binding of mCRP to enzymatically-modified low-density lipoprotein (E-LDL).


RESULTS
mCRP was approximately 60 times more potent than CRP in binding to E-LDL. In the presence of the small-molecule compound phosphoethanolamine (PEt), at 37 degrees C, the binding of mCRP to E-LDL was enhanced <2-fold, while the binding of CRP to E-LDL was enhanced >10-fold. In contrast, PEt inhibited the binding of both CRP and mCRP to pneumococcal C-polysaccharide, another phosphocholine-containing ligand to which CRP and mCRP were found to bind. We have not investigated yet whether PEt alters the structure of CRP at 37 degrees C.


CONCLUSIONS
Combined data suggest that the targeting of CRP with the aim to monomerize CRP in vivo may be an effective approach to capture modified forms of LDL.
Singh
Sanjay K
SK
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Suresh
Madathilparambil V
MV
Hammond
David J
DJ
Rusiñol
Antonio E
AE
Potempa
Lawrence A
LA
Agrawal
Alok
A
D000818:Animals; D002097:C-Reactive Protein / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism*
D004983:Ethanolamines; D008077:Lipoproteins, LDL; D011135:Polysaccharides, Bacterial; C027158:polysaccharide C-substance (Streptococcus); C005448:phosphorylethanolamine; D002097:C-Reactive Protein; D002787:Sterol Esterase