Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q.
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 regi...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797101873498423296 |
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| author | Roumenina, LT Kantardjiev, A Atanasov, B Waters, P Gadjeva, M Reid, K Mantovani, A Kishore, U Kojouharova, MS |
| author_facet | Roumenina, LT Kantardjiev, A Atanasov, B Waters, P Gadjeva, M Reid, K Mantovani, A Kishore, U Kojouharova, MS |
| author_sort | Roumenina, LT |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:58:06Z |
| format | Journal article |
| id | oxford-uuid:eb38aa7b-7a0e-4da3-9022-fefec9ee13e2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:58:06Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:eb38aa7b-7a0e-4da3-9022-fefec9ee13e22022-03-27T11:08:04ZRole of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:eb38aa7b-7a0e-4da3-9022-fefec9ee13e2EnglishSymplectic Elements at Oxford2005Roumenina, LTKantardjiev, AAtanasov, BWaters, PGadjeva, MReid, KMantovani, AKishore, UKojouharova, MSC1q 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. |
| spellingShingle | Roumenina, LT Kantardjiev, A Atanasov, B Waters, P Gadjeva, M Reid, K Mantovani, A Kishore, U Kojouharova, MS Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title | Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title_full | Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title_fullStr | Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title_full_unstemmed | Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title_short | Role of Ca2+ in the electrostatic stability and the functional activity of the globular domain of human C1q. |
| title_sort | role of ca2 in the electrostatic stability and the functional activity of the globular domain of human c1q |
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