GC1q-R/p33: Structure-function predictions from the crystal structure

被引:49
作者
Ghebrehiwet, B [1 ]
Jesty, J
Peerschke, EIB
机构
[1] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA
[2] Cornell Univ, Weill Med Coll, Dept Pathol, New York, NY USA
关键词
D O I
10.1078/0171-2985-00143
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human gC1q-R (p33) is a multicompartmental cellular protein expressed oil various types of cells and tissues. Although originally isolated as a receptor for C1q by virtue of its specificity for the globular heads of that molecule, a large body of evidence has now been accumulated which shows that in addition to C1q, gC1q-R can serve as a receptor for diverse ligands including proteins of the intrinsic coagulation/bradykinin forming cascade, as well as antigens of cellular, bacterial, and viral origin. Furthermore, since gC1q-R has been shown to regulate the functions of protein kinase C (PKC), it is postulated that gC1q-R-induced signaling cascade may involve activation of PKC. These data collectively therefore suggest that gC1q-R plays an important role in blood coagulation, inflammation, and infection. However, although significant progress has been made in unraveling the molecular, biochemical, and structural features of this molecule, and data in support of its biological relevance is accumulating, it is still unclear as to how the molecule is anchored on the membrane since its sequence is devoid of a classical transmembrane domain or a glycosylphosphatidylinositol (GPI) anchor. Furthermore, while recombinant gC1q-R can bind to cell surfaces suggesting that it may bind directly to the phospholipid bilayer, our recent experiments show that, at least in vitro, gC1q-R does not bind to unilamellar vesicle preparations of either phosphatidylcholine (PC) or phosphatidylserine: phosphatidylcholine. This work was therefore undertaken to analyze the three-dimensional structure of gC1q-R in order to identify unique structural features that may serve not only to anchor the protein but also to explain its affinity for such a diversity of plasma as well as microbial and viral ligands.
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页码:421 / 432
页数:12
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