Serine 132 Is the C3 Covalent Attachment Point on the CH1 Domain of Human IgG1

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dc.contributor.authorVidarte, Luis
dc.contributor.authorPastor Vargas, Carlos
dc.contributor.authorMas, Sebastian
dc.contributor.authorBlázquez, Ana Belen
dc.contributor.authorRios, Vivian de los
dc.contributor.authorGuerrero, Rosa
dc.contributor.authorVivanco Martínez, Fernando
dc.date.accessioned2024-01-15T10:54:55Z
dc.date.available2024-01-15T10:54:55Z
dc.date.issued2001
dc.description.abstractThe covalent binding of C3 (complement component C3) to antigen-antibody complexes (Ag.Ab; immune complexes (ICs)) is a key event in the uptake, transport, presentation, and elimination of Ag in the form of Ag.Ab.C3b (IC.C3b). Upon interaction of C3 with IgG.IC, C3b.C3b.IgG covalent complexes are formed that are detected on SDS-polyacrylamide gel electrophoresis by two bands corresponding to C3b.C3b (band A) and C3b.IgG (band B) covalent complexes. This allows one to evaluate the covalent binding of C3b to IgG antibodies. It has been described that C3b can attach to both the Fab (on the CH1 domain) and the Fc regions of IgG. Here the covalent interaction of C3b to the CH1 domain, a region previously described spanning residues 125-147, has been studied. This region of the CH1 domain is exposed to solvent and contains a cluster of six potential acceptor sites for ester bond formation with C3b (four Ser and two Thr). A set of 10 mutant Abs were generated with the putative acceptor residues substituted by Ala, and we studied their covalent interaction with C3b. Single (Ser-131, Ser-132, Ser-134, Thr-135, Ser-136, and Thr-139), double (positions 131-132), and multiple (positions 134-135-136, 131-132-134-135-136, and 131-132-134-135-136-139) mutants were produced. None of the mutants (single, double, or multiple) abolished completely the ability of IgG to bind C3b, indicating the presence of C3b binding regions other than in the CH1 domain. However, all mutant Abs, in which serine at position 132 was replaced by Ala, showed a significant decrease in the ability to form C3b.IgG covalent complexes, whereas the remaining mutants had normal activity. In addition we examined ICs using the F(ab')2 fragment of the mutant Abs, and only those containing Ala at position 132 (instead of Ser) failed to bind C3b. Thus Ser-132 is the binding site for C3b on the CH1 domain of the heavy chain, in the Fab region of human IgG.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationVidarte L, Pastor C, Mas S, Blázquez AB, de los Rios V, Guerrero R, Vivanco F. Serine 132 is the C3 covalent attachment point on the CH1 domain of human IgG1. J Biol Chem. 2001 Oct 12;276(41):38217-23. doi: 10.1074/jbc.M104870200. Epub 2001 Jul 10. PMID: 11447230.
dc.identifier.doi10.1074/jbc.m104870200
dc.identifier.issn0021-9258
dc.identifier.officialurlhttps://doi.org/10.1074/jbc.M104870200
dc.identifier.pmid11447230
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93016
dc.issue.number41
dc.journal.titleJournal of Biological Chemistry
dc.language.isoeng
dc.page.final38223
dc.page.initial38217
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.1
dc.subject.keywordAntibodies
dc.subject.keywordChemical bonds
dc.subject.keywordComplexation
dc.subject.keywordImmunology
dc.subject.keywordMutagenesis
dc.subject.keywordSolvents
dc.subject.ucmBioquímica (Química)
dc.subject.unesco2302 Bioquímica
dc.titleSerine 132 Is the C3 Covalent Attachment Point on the CH1 Domain of Human IgG1
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number276
dspace.entity.typePublication
relation.isAuthorOfPublication25af78c7-0077-4891-a14e-bcd8e51fe408
relation.isAuthorOfPublication6f3e7679-cbc7-4f23-8355-2de0876d46ad
relation.isAuthorOfPublication.latestForDiscovery25af78c7-0077-4891-a14e-bcd8e51fe408
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