Methionine oxidation in human IgG2 Fc decreases binding affinities to protein A and FcRn
| Autor: | Hai Pan, Liping Chu, Izydor Apostol, Kenneth Chen, Francis Kinderman, Gang Huang |
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| Rok vydání: | 2009 |
| Předmět: |
Molecular Sequence Data
Antibody Affinity CHO Cells Receptors Fc Plasma protein binding Biochemistry Article Residue (chemistry) chemistry.chemical_compound Cricetulus Methionine tert-Butylhydroperoxide Cricetinae Animals Amino Acid Sequence Binding site Staphylococcal Protein A Molecular Biology Peptide sequence biology Chemistry Chinese hamster ovary cell Histocompatibility Antigens Class I Immunoglobulin Fc Fragments Hydrogen-Ion Concentration Kinetics Immobilized Proteins Immunoglobulin G biology.protein Protein A Oxidation-Reduction Sequence Alignment Protein Binding |
| Zdroj: | Protein Science. 18:424-433 |
| ISSN: | 1469-896X 0961-8368 |
| Popis: | Susceptibility of methionine residues to oxidation is a significant issue of protein therapeutics. Methionine oxidation may limit the product's clinical efficacy or stability. We have studied kinetics of methionine oxidation in the Fc portion of the human IgG2 and its impact on the interaction with FcRn and Protein A. Our results confirm previously published observations for IgG1 that two analogous solvent-exposed methionine residues in IgG2, Met 252 and Met 428, oxidize more readily than the other methionine residue, Met 358, which is buried inside the Fc. Met 397, which is not present in IgG1 but in IgG2, oxidizes at similar rate as Met 358. Oxidation of two labile methionines, Met 252 and Met 428, weakens the binding of the intact antibody with Protein A and FcRn, two natural protein binding partners. Both of these binding partners share the same binding site on the Fc. Additionally, our results shows that Protein A may serve as a convenient and inexpensive surrogate for FcRn binding measurements. |
| Databáze: | OpenAIRE |
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