Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q

Lubka T. Roumenina, Alexandar A. Kantardjiev, Boris P. Atanasov, Patrick Waters, Mihaela Gadjeva, Kenneth B M Reid, Alberto Mantovani, Uday Kishore, Mihaela S. Kojouharova

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

C1q is the recognition subunit of the classical pathway of the complement system and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM-mediated acquired immunity. The basic structural subunit of C1q is composed of an N-terminal triple-helical collagen-like region and a C-terminal heterotrimeric globular head domain (gC1q) that is made up of individual A, B, and C chains. Recent crystallographic studies have revealed that the gC1q domain, which is the main target-binding region of C1q, has a compact and spherical heterotrimeric assembly, held together by both electrostatic and nonpolar interactions, with quasi-3-fold symmetry. A characteristic feature of the gC1q domain is the presence of a exposed Ca 2+ located near the apex. We have investigated, using theoretical and experimental approaches, the role of Ca2+ in the electrostatic stability and target-binding properties of the native C1q as well as recombinant monomeric forms of the C-terminal regions of the A, B, and C chains. Here, we report that Ca2+ primarily influences the target recognition properties of C1q toward IgG, IgM, C-reactive protein, and pentraxin 3. At pH 7.4, the loss of Ca2+ leads to changes in the direction of electric moment from coaxial (where the putative C-reactive protein-binding site is located) to perpendicular to the molecular axis (toward the most likely IgG-binding site), which appears important for target recognition by C1q and subsequent complement activation.

Original languageEnglish
Pages (from-to)14097-14109
Number of pages13
JournalBiochemistry
Volume44
Issue number43
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Static Electricity
Electrostatics
Immunoglobulin G
C-Reactive Protein
Immunoglobulin M
Complement C1q
Binding Sites
Classical Complement Pathway
Complement Activation
Adaptive Immunity
Innate Immunity
Protein Binding
Collagen
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Roumenina, L. T., Kantardjiev, A. A., Atanasov, B. P., Waters, P., Gadjeva, M., Reid, K. B. M., ... Kojouharova, M. S. (2005). Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. Biochemistry, 44(43), 14097-14109. https://doi.org/10.1021/bi051186n

Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. / Roumenina, Lubka T.; Kantardjiev, Alexandar A.; Atanasov, Boris P.; Waters, Patrick; Gadjeva, Mihaela; Reid, Kenneth B M; Mantovani, Alberto; Kishore, Uday; Kojouharova, Mihaela S.

In: Biochemistry, Vol. 44, No. 43, 01.11.2005, p. 14097-14109.

Research output: Contribution to journalArticle

Roumenina, LT, Kantardjiev, AA, Atanasov, BP, Waters, P, Gadjeva, M, Reid, KBM, Mantovani, A, Kishore, U & Kojouharova, MS 2005, 'Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q', Biochemistry, vol. 44, no. 43, pp. 14097-14109. https://doi.org/10.1021/bi051186n
Roumenina LT, Kantardjiev AA, Atanasov BP, Waters P, Gadjeva M, Reid KBM et al. Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. Biochemistry. 2005 Nov 1;44(43):14097-14109. https://doi.org/10.1021/bi051186n
Roumenina, Lubka T. ; Kantardjiev, Alexandar A. ; Atanasov, Boris P. ; Waters, Patrick ; Gadjeva, Mihaela ; Reid, Kenneth B M ; Mantovani, Alberto ; Kishore, Uday ; Kojouharova, Mihaela S. / Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. In: Biochemistry. 2005 ; Vol. 44, No. 43. pp. 14097-14109.
@article{15b0cf6eda1745cfb11e64cd6778d0f1,
title = "Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q",
abstract = "C1q is the recognition subunit of the classical pathway of the complement system and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM-mediated acquired immunity. The basic structural subunit of C1q is composed of an N-terminal triple-helical collagen-like region and a C-terminal heterotrimeric globular head domain (gC1q) that is made up of individual A, B, and C chains. Recent crystallographic studies have revealed that the gC1q domain, which is the main target-binding region of C1q, has a compact and spherical heterotrimeric assembly, held together by both electrostatic and nonpolar interactions, with quasi-3-fold symmetry. A characteristic feature of the gC1q domain is the presence of a exposed Ca 2+ located near the apex. We have investigated, using theoretical and experimental approaches, the role of Ca2+ in the electrostatic stability and target-binding properties of the native C1q as well as recombinant monomeric forms of the C-terminal regions of the A, B, and C chains. Here, we report that Ca2+ primarily influences the target recognition properties of C1q toward IgG, IgM, C-reactive protein, and pentraxin 3. At pH 7.4, the loss of Ca2+ leads to changes in the direction of electric moment from coaxial (where the putative C-reactive protein-binding site is located) to perpendicular to the molecular axis (toward the most likely IgG-binding site), which appears important for target recognition by C1q and subsequent complement activation.",
author = "Roumenina, {Lubka T.} and Kantardjiev, {Alexandar A.} and Atanasov, {Boris P.} and Patrick Waters and Mihaela Gadjeva and Reid, {Kenneth B M} and Alberto Mantovani and Uday Kishore and Kojouharova, {Mihaela S.}",
year = "2005",
month = "11",
day = "1",
doi = "10.1021/bi051186n",
language = "English",
volume = "44",
pages = "14097--14109",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "43",

}

TY - JOUR

T1 - Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q

AU - Roumenina, Lubka T.

AU - Kantardjiev, Alexandar A.

AU - Atanasov, Boris P.

AU - Waters, Patrick

AU - Gadjeva, Mihaela

AU - Reid, Kenneth B M

AU - Mantovani, Alberto

AU - Kishore, Uday

AU - Kojouharova, Mihaela S.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - C1q is the recognition subunit of the classical pathway of the complement system and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM-mediated acquired immunity. The basic structural subunit of C1q is composed of an N-terminal triple-helical collagen-like region and a C-terminal heterotrimeric globular head domain (gC1q) that is made up of individual A, B, and C chains. Recent crystallographic studies have revealed that the gC1q domain, which is the main target-binding region of C1q, has a compact and spherical heterotrimeric assembly, held together by both electrostatic and nonpolar interactions, with quasi-3-fold symmetry. A characteristic feature of the gC1q domain is the presence of a exposed Ca 2+ located near the apex. We have investigated, using theoretical and experimental approaches, the role of Ca2+ in the electrostatic stability and target-binding properties of the native C1q as well as recombinant monomeric forms of the C-terminal regions of the A, B, and C chains. Here, we report that Ca2+ primarily influences the target recognition properties of C1q toward IgG, IgM, C-reactive protein, and pentraxin 3. At pH 7.4, the loss of Ca2+ leads to changes in the direction of electric moment from coaxial (where the putative C-reactive protein-binding site is located) to perpendicular to the molecular axis (toward the most likely IgG-binding site), which appears important for target recognition by C1q and subsequent complement activation.

AB - C1q is the recognition subunit of the classical pathway of the complement system and a major connecting link between classical pathway-driven innate immunity and IgG- or IgM-mediated acquired immunity. The basic structural subunit of C1q is composed of an N-terminal triple-helical collagen-like region and a C-terminal heterotrimeric globular head domain (gC1q) that is made up of individual A, B, and C chains. Recent crystallographic studies have revealed that the gC1q domain, which is the main target-binding region of C1q, has a compact and spherical heterotrimeric assembly, held together by both electrostatic and nonpolar interactions, with quasi-3-fold symmetry. A characteristic feature of the gC1q domain is the presence of a exposed Ca 2+ located near the apex. We have investigated, using theoretical and experimental approaches, the role of Ca2+ in the electrostatic stability and target-binding properties of the native C1q as well as recombinant monomeric forms of the C-terminal regions of the A, B, and C chains. Here, we report that Ca2+ primarily influences the target recognition properties of C1q toward IgG, IgM, C-reactive protein, and pentraxin 3. At pH 7.4, the loss of Ca2+ leads to changes in the direction of electric moment from coaxial (where the putative C-reactive protein-binding site is located) to perpendicular to the molecular axis (toward the most likely IgG-binding site), which appears important for target recognition by C1q and subsequent complement activation.

UR - http://www.scopus.com/inward/record.url?scp=27544443735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27544443735&partnerID=8YFLogxK

U2 - 10.1021/bi051186n

DO - 10.1021/bi051186n

M3 - Article

C2 - 16245926

AN - SCOPUS:27544443735

VL - 44

SP - 14097

EP - 14109

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 43

ER -