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

Roumenina, LT; Kantardjiev, A; Atanasov, B; Waters, P; Gadjeva, M; Reid, K; Mantovani, A; Kishore, U; Kojouharova, MS

Journal article

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 Ca(2+) 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 Ca(2+) primarily influences the target recognition properties of C1q toward IgG, IgM, C-reactive protein, and pentraxin 3. At pH 7.4, the loss of Ca(2+) 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.

Publication status:: Published

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APA Style

Roumenina, L. T., Kantardjiev, A., Atanasov, B., Waters, P., Gadjeva, M., Reid, K., Mantovani, A., Kishore, U., & 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.

MLA Style

Roumenina, LT, et al. “Role of Ca2+ in the Electrostatic Stability and the Functional Activity of the Globular Domain of Human C1q.” Biochemistry, vol. 44, no. 43, 2005, pp. 14097–109.

Chicago Style

Roumenina, LT, A Kantardjiev, B Atanasov, et al. 2005. “Role of Ca2+ in the Electrostatic Stability and the Functional Activity of the Globular Domain of Human C1q.” Biochemistry 44 (43): 14097–109.
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