Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A disulphide-constrained peptide that binds to the low affinity Fc receptor, FcgammaRIIa (CD32) has been identified and its structure solved by NMR. Linear (7-mer and 12-mer) and disulphide-constrained (7-mer) phage display peptide libraries were panned on recombinant soluble FcgammaRIIa genetically fused to HSA (HSA-FcgammaRIIa). Peptides were isolated only from the constrained peptide library and these contained the consensus sequence, CWPGWxxC. Phage clones displaying variants of the peptide consensus sequence bound to FcgammaRIIa and the strongest binding clone C7C1 (CWPGWDLNC) competed with IgG for binding to FcgammaRIIa and was inhibited from binding to FcgammaRIIa by the FcgammaRIIa-blocking antibody, IV.3, suggesting that C7C1 and IgG share related binding sites on FcgammaRIIa. A synthetic disulphide-constrained peptide, pep-C7C1 bound to FcgammaRIIa by biosensor analysis, albeit with low affinity (KD approximately 100microM). It was significant that the FcgammaRIIa consensus peptide sequence contained a Proline (Pro3), which when substituted with alanine abrogated FcgammaRIIa binding, consistent with Pro3 contributing to receptor binding. Upon binding of IgG and IgE to their respective Fc receptors (FcgammaRs and FcepsilonRI) Pro329 in the Fc makes a critical interaction with two highly conserved Trp residues (Trp90 and Trp113) of the FcRs. The NMR structure of pep-C7C1 revealed a stabilizing type II beta-turn between Trp2 and Trp5, with Pro3 solvent exposed. Modelling of the pep-C7C1 structure in complex with FcgammaRIIa suggests that Pro3 of C7C1 binds to FcgammaRIIa by inserting between Trp90 and Trp113 of FcgammaRIIa thereby mimicking the molecular interaction made between FcgammaRIIa and IgG.
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PMID:An FcgammaRIIa-binding peptide that mimics the interaction between FcgammaRIIa and IgG. 1767 95

Modified C-reactive protein (mCRP) has been reported to non-specifically bind to immunoglobulins; notwithstanding, the nature of these interactions is not clear. The aim of this study was to investigate the binding of antibodies directed against HSA and IgG to mCRP, fibrinogen (Fg), IgG, fibronectin (Fn) and C1q and its contaminants. We also studied the binding of mCRP to the antibodies directed towards receptors involved in CRP signalling (anti-CD32, anti-CD16). For the analysis of such interactions, a combination of ELISA and Western immunoblotting has been applied. The tested antibodies powerfully bound to either the contaminations of purified proteins (Fg, IgG, Fn and mCRP) or interacted directly with some of these proteins (C1q, mCRP, Fg). The effectiveness of anti-HSA binding to immobilized proteins was influenced by the antigenic specificity of the antibody, the content of various protein fractions in the contaminants of a given protein (albumin augmented the interactions), overall protein purity and a natural avidity of a given protein towards immunoglobulins. The relative binding of anti-HSA or anti-IgG to immobilized mCRP was considerably lower than that observed for plasma proteins. Furthermore, the strength of the direct interaction between immunoglobulins and mCRP varied from the lack of response (anti-HSA) or a negligible response (anti-IgG) to the relatively high signal (human IgG, anti-CD16, anti-CD32), as compared to the control. Based on these observations, we conclude that the binding of mCRP to immunoglobulins cannot be easily generalized as a kind of some universal phenomenon.
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PMID:Modified C-reactive protein selectively binds to immunoglobulins. 2248 30