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Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q

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Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. / Zlatarova, Alexandra S; Rouseva, Marieta; Roumenina, Lubka T; Gadjeva, Mihaela; Kolev, Martin; Dobrev, Ivan; Olova, Neli; Ghai, Rohit; Jensenius, Jens Christian; Reid, Kenneth B M; Kishore, Uday; Kojouharova, Mihaela S.

In: Biochemistry, Vol. 45, No. 33, 2006, p. 9979-88.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Zlatarova, AS, Rouseva, M, Roumenina, LT, Gadjeva, M, Kolev, M, Dobrev, I, Olova, N, Ghai, R, Jensenius, JC, Reid, KBM, Kishore, U & Kojouharova, MS 2006, 'Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q', Biochemistry, vol. 45, no. 33, pp. 9979-88. https://doi.org/10.1021/bi060539v

APA

Zlatarova, A. S., Rouseva, M., Roumenina, L. T., Gadjeva, M., Kolev, M., Dobrev, I., Olova, N., Ghai, R., Jensenius, J. C., Reid, K. B. M., Kishore, U., & Kojouharova, M. S. (2006). Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. Biochemistry, 45(33), 9979-88. https://doi.org/10.1021/bi060539v

CBE

Zlatarova AS, Rouseva M, Roumenina LT, Gadjeva M, Kolev M, Dobrev I, Olova N, Ghai R, Jensenius JC, Reid KBM, Kishore U, Kojouharova MS. 2006. Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. Biochemistry. 45(33):9979-88. https://doi.org/10.1021/bi060539v

MLA

Vancouver

Zlatarova AS, Rouseva M, Roumenina LT, Gadjeva M, Kolev M, Dobrev I et al. Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. Biochemistry. 2006;45(33):9979-88. https://doi.org/10.1021/bi060539v

Author

Zlatarova, Alexandra S ; Rouseva, Marieta ; Roumenina, Lubka T ; Gadjeva, Mihaela ; Kolev, Martin ; Dobrev, Ivan ; Olova, Neli ; Ghai, Rohit ; Jensenius, Jens Christian ; Reid, Kenneth B M ; Kishore, Uday ; Kojouharova, Mihaela S. / Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q. In: Biochemistry. 2006 ; Vol. 45, No. 33. pp. 9979-88.

Bibtex

@article{5b4a07f61f2a4a3db3dd72387bb21341,
title = "Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q",
abstract = "C1q is the first subcomponent of the classical complement pathway that binds antigen-bound IgG or IgM and initiates complement activation via association of serine proteases C1r and C1s. The globular domain of C1q (gC1q), which is the ligand-recognition domain, is a heterotrimeric structure composed of the C-terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and functional characterization of ghA, ghB, and ghC modules have revealed that each chain has some structural and functional autonomy. Although a number of studies have tried to identify IgG-binding sites on the gC1q domain, no such attempt has been made to localize IgM-binding site. On the basis of the information available via the gC1q crystal structure, molecular modeling, mutational studies, and bioinformatics, we have generated a series of substitution mutants of ghA, ghB, and ghC and examined their interactions with IgM. The comparative analysis of IgM- and IgG-binding abilities of the mutants suggests that the IgG- and IgM-binding sites within the gC1q domain are different but may overlap. Whereas Arg(B108), Arg (B109), and Tyr(B175) mainly constitute the IgM-binding site, the residues Arg(B114), Arg(B129), Arg(B163), and His(B117) that have been shown to be central to IgG binding are not important for the C1q-IgM interaction. Given the location of Arg(B108), Arg (B109), and Tyr(B175) in the gC1q crystal structure, it is likely that C1q interacts with IgM via the top of the gC1q domain.",
keywords = "Arginine, Binding Sites, Complement C1q, Computational Biology, Crystallography, X-Ray, Humans, Hydrogen-Ion Concentration, Immunoglobulin G, Immunoglobulin M, Ligands, Models, Molecular, Point Mutation, Protein Folding, Protein Subunits, Recombinant Proteins, Tyrosine",
author = "Zlatarova, {Alexandra S} and Marieta Rouseva and Roumenina, {Lubka T} and Mihaela Gadjeva and Martin Kolev and Ivan Dobrev and Neli Olova and Rohit Ghai and Jensenius, {Jens Christian} and Reid, {Kenneth B M} and Uday Kishore and Kojouharova, {Mihaela S}",
year = "2006",
doi = "10.1021/bi060539v",
language = "English",
volume = "45",
pages = "9979--88",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "ACS Publications",
number = "33",

}

RIS

TY - JOUR

T1 - Existence of different but overlapping IgG- and IgM-binding sites on the globular domain of human C1q

AU - Zlatarova, Alexandra S

AU - Rouseva, Marieta

AU - Roumenina, Lubka T

AU - Gadjeva, Mihaela

AU - Kolev, Martin

AU - Dobrev, Ivan

AU - Olova, Neli

AU - Ghai, Rohit

AU - Jensenius, Jens Christian

AU - Reid, Kenneth B M

AU - Kishore, Uday

AU - Kojouharova, Mihaela S

PY - 2006

Y1 - 2006

N2 - C1q is the first subcomponent of the classical complement pathway that binds antigen-bound IgG or IgM and initiates complement activation via association of serine proteases C1r and C1s. The globular domain of C1q (gC1q), which is the ligand-recognition domain, is a heterotrimeric structure composed of the C-terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and functional characterization of ghA, ghB, and ghC modules have revealed that each chain has some structural and functional autonomy. Although a number of studies have tried to identify IgG-binding sites on the gC1q domain, no such attempt has been made to localize IgM-binding site. On the basis of the information available via the gC1q crystal structure, molecular modeling, mutational studies, and bioinformatics, we have generated a series of substitution mutants of ghA, ghB, and ghC and examined their interactions with IgM. The comparative analysis of IgM- and IgG-binding abilities of the mutants suggests that the IgG- and IgM-binding sites within the gC1q domain are different but may overlap. Whereas Arg(B108), Arg (B109), and Tyr(B175) mainly constitute the IgM-binding site, the residues Arg(B114), Arg(B129), Arg(B163), and His(B117) that have been shown to be central to IgG binding are not important for the C1q-IgM interaction. Given the location of Arg(B108), Arg (B109), and Tyr(B175) in the gC1q crystal structure, it is likely that C1q interacts with IgM via the top of the gC1q domain.

AB - C1q is the first subcomponent of the classical complement pathway that binds antigen-bound IgG or IgM and initiates complement activation via association of serine proteases C1r and C1s. The globular domain of C1q (gC1q), which is the ligand-recognition domain, is a heterotrimeric structure composed of the C-terminal regions of A (ghA), B (ghB), and C (ghC) chains. The expression and functional characterization of ghA, ghB, and ghC modules have revealed that each chain has some structural and functional autonomy. Although a number of studies have tried to identify IgG-binding sites on the gC1q domain, no such attempt has been made to localize IgM-binding site. On the basis of the information available via the gC1q crystal structure, molecular modeling, mutational studies, and bioinformatics, we have generated a series of substitution mutants of ghA, ghB, and ghC and examined their interactions with IgM. The comparative analysis of IgM- and IgG-binding abilities of the mutants suggests that the IgG- and IgM-binding sites within the gC1q domain are different but may overlap. Whereas Arg(B108), Arg (B109), and Tyr(B175) mainly constitute the IgM-binding site, the residues Arg(B114), Arg(B129), Arg(B163), and His(B117) that have been shown to be central to IgG binding are not important for the C1q-IgM interaction. Given the location of Arg(B108), Arg (B109), and Tyr(B175) in the gC1q crystal structure, it is likely that C1q interacts with IgM via the top of the gC1q domain.

KW - Arginine

KW - Binding Sites

KW - Complement C1q

KW - Computational Biology

KW - Crystallography, X-Ray

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Immunoglobulin G

KW - Immunoglobulin M

KW - Ligands

KW - Models, Molecular

KW - Point Mutation

KW - Protein Folding

KW - Protein Subunits

KW - Recombinant Proteins

KW - Tyrosine

U2 - 10.1021/bi060539v

DO - 10.1021/bi060539v

M3 - Journal article

C2 - 16906756

VL - 45

SP - 9979

EP - 9988

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 33

ER -