@article{66f776bbde754b659c18184652a973bc,
title = "Ligand binding specificity of a rabbit alveolar macrophage receptor for C3b",
abstract = "We have recently reported the isolation from rabbit alveolar macrophages of a receptor which retained its ligand-binding activity for the third component of complement (C3) and for its major proteolytic derived activation fragment (C3b). The isolated receptor demonstrated a greater ability to bind C3b than an equimolar amount of C3. C3b differs from C3 in at least two ways: it is a proteolytic cleavage product of C3 and it lacks the internal thiolester bond of C3. We have analyzed the binding ability of isolated receptor to various C3 and C3b analogs and we demonstrate that the specificity of the C3b-C3b receptor interaction depends upon the lysis of the C3 thiolester bond and accompanying conformational change rather than upon proteolytic cleavage of the C3 molecule. Minimal, if any, binding of C3 with an intact thiolester bond to the isolated receptor was demonstrable.",
author = "R. Dixit and R. Schneider and Law, {S. K.} and A. Kulczycki and Atkinson, {J. P.}",
note = "Funding Information: *Children{\textquoteright}s Hcspital Research Foundation, Cincinnati, OH 45229 and Children{\textquoteright}s Hospital Medical Center, Boston, MA 02115. In addition to regulating CT CTINH also inhibits activated Hageman factor (Factor Xlla), activated PTA (Factor Xla), kallikrein and plasmin. To evaluate the functions of CTINH in unfractionated normal p&ma, plasma was depleted of CTINH with monospecific antibody globulins directed against Cl-INH, and residual amounts of each procoagulant and of plasminoaen were then auantified. Immune adsorption of normal plasma depleted it of_CTINH in proportion lo the amount{\textquoteright}of antibody used, diminished the plasma concentrations of prekallikrein (Fletcher factor), high molecular weight kininogen and PTA, but not of liageman factor, even after its activation. Plasminogen was not removed by immue adsorption of plasma, but following activation by streptokinase its concentration was decreased. The removal of PTA and high molecular weight kininogen was dependent upon the presence of prekallikrein; neither was removed from prekallikrein-deficient plasma by adsorption with the anti-Cl-INH. Three different types of dysmorphic CFINkproteins in plasma from patients with hereditary angioneurotic edema were depleted by anti-ClINH, but none of the procoagulants measured or plasminogen was removed. Once plasma was treated with streptokinase, the concentra-tign of plasminogen was depleted by the immue adsorption. Theeffect of immune adsorption with anti-Cl-INH was specific, and not due to an immune precipitate in the plasma, for antibody to clotting Fac-toLVlll or fibrinogen did not reduce the plasma concentrations of the clotting factors measured, or of Cl-INH to a detectable degree. (Supported by USPHS Grants HLB-15690 and Al-05877) HYDROLYSiS AND AMINOLYSIS OF MACROCYCLIC PEPTIDE THtOLACTONES RELATED TO THE METASTABLE BINDING SITE OF C3b. Bruce W. Erickson{\textquoteright} and Shabbir A. Khan, The Rockefeller University, New York, New York 10021, The nucleophilic cleavage of two macrocyclic hexapeptide thiolesters (R-Gl~Cys-Gly-Glu-Glu-AsnNH2, R = H of CH3CO) that are part of the metastable binding site of C3b has been examined under physiologic conditions (veronal-buffered saline, pli 7.3, 37°C). NMR studies suggest that in acid the novel 1, 5, 8, ll-thiatriazacyclopentadecane ring of the acetylated thiolactone exists in a single relatively rigid conformation. Its activation energy for hydrolysis is about 5 kcallmol lower than that for hydrolysis of the acyclic thiolester, N, S-di-acetyl-L-cysteine methylamide. In the absence of amines, the thiolactones are hydrolyzed 2000-3000 times faster (t%, = 10 min) than the acyclic thiolester. In 0.3 M methylamine, their net rates of aminolysis are about 70 times faster than that of the acyclic model. Both reactions are first order in hydroxide ion. Hydrolysis is enhanced marginally by 0.1 M triethylamine or I-methylimidazoie but significantly by 0.1 M 2-methylimjd~ole, imidazole, or N-acetyl-L-histidine. Cleavage of the thiolactone ring was not enhanced by the presence of ~-acetyl-L-serine methylamide or ~-methyl-D-mannoside. The 15-membered thiolactone ring is probably necessary but not sufficient to explain the reactivity of the metastable binding site of C3b. (Supported in part by USPHS grants Al 15301 and CA 24435 and by Shell Development Corporation.)",
year = "1982",
language = "English",
volume = "257",
pages = "1595--1597",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
number = "4",
}