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 language | English |
|---|---|
| Pages (from-to) | 14097-14109 |
| Number of pages | 13 |
| Journal | Biochemistry |
| Volume | 44 |
| Issue number | 43 |
| DOIs | |
| Publication status | Published - Nov 1 2005 |
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- Biochemistry
Cite this
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 journal › Article
}
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.
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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 -