کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5918051 1163825 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An FcγRIIa-binding peptide that mimics the interaction between FcγRIIa and IgG
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
An FcγRIIa-binding peptide that mimics the interaction between FcγRIIa and IgG
چکیده انگلیسی

A disulphide-constrained peptide that binds to the low affinity Fc receptor, FcγRIIa (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 FcγRIIa genetically fused to HSA (HSA-FcγRIIa). 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 FcγRIIa and the strongest binding clone C7C1 (CWPGWDLNC) competed with IgG for binding to FcγRIIa and was inhibited from binding to FcγRIIa by the FcγRIIa-blocking antibody, IV.3, suggesting that C7C1 and IgG share related binding sites on FcγRIIa. A synthetic disulphide-constrained peptide, pep-C7C1 bound to FcγRIIa by biosensor analysis, albeit with low affinity (KD ∼ 100 μM). It was significant that the FcγRIIa consensus peptide sequence contained a Proline (Pro3), which when substituted with alanine abrogated FcγRIIa binding, consistent with Pro3 contributing to receptor binding. Upon binding of IgG and IgE to their respective Fc receptors (FcγRs and FcɛRI) 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 β-turn between Trp2 and Trp5, with Pro3 solvent exposed. Modelling of the pep-C7C1 structure in complex with FcγRIIa suggests that Pro3 of C7C1 binds to FcγRIIa by inserting between Trp90 and Trp113 of FcγRIIa thereby mimicking the molecular interaction made between FcγRIIa and IgG.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 45, Issue 2, January 2008, Pages 307-319
نویسندگان
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