An Intrinsically Disordered Motif Mediates Diverse Actions of Monomeric C-reactive Protein.

The Journal of Biological Chemistry
Hai-Yun LiY Wu

Abstract

Most proinflammatory actions of C-reactive protein (CRP) are only expressed following dissociation of its native pentameric assembly into monomeric form (mCRP). However, little is known about what underlies the greatly enhanced activities of mCRP. Here we show that a single sequence motif, i.e. cholesterol binding sequence (CBS; a.a. 35-47), is responsible for mediating the interactions of mCRP with diverse ligands. The binding of mCRP to lipoprotein component ApoB, to complement component C1q, to extracellular matrix components fibronectin and collagen, to blood coagulation component fibrinogen, and to membrane lipid component cholesterol, are all found to be markedly inhibited by the synthetic CBS peptide but not by other CRP sequences tested. Likewise, mutating CBS in mCRP also greatly impairs these interactions. Functional experiments further reveal that CBS peptide significantly reduces the effects of mCRP on activation of endothelial cells in vitro and on acute induction of IL-6 in mice. The potency and specificity of CBS are critically determined by the N-terminal residues Cys-36, Leu-37, and His-38; while the versatility of CBS appears to originate from its intrinsically disordered conformation polymorphism. Together, t...Continue Reading

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Citations

Jun 2, 2017·Journal of the American Society of Nephrology : JASN·Qiu-Yu LiMing-Hui Zhao
Jun 4, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Magdalena BonclerCezary Watala
Jul 18, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·ZhenYu YaoHaiBin Wu
Jan 18, 2017·The Journal of Biological Chemistry·Sanjay K SinghAlok Agrawal
Aug 6, 2019·Frontiers in Immunology·Sanjay K Singh, Alok Agrawal
Mar 30, 2018·Frontiers in Immunology·Lin ZhangYi Wu
May 23, 2019·Frontiers in Immunology·Asmita Pathak, Alok Agrawal
Mar 14, 2019·Frontiers in Immunology·Donald N Ngwa, Alok Agrawal
Nov 26, 2019·Molecular Immunology·Naeem UllahHai-Yun Li
Dec 17, 2020·Frontiers in Immunology·Peter C HartLawrence A Potempa
Sep 3, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chitose FujitaMasaaki Fujita

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