Thermodynamic, conformational and functional properties of the human C1q globular heads in the intact C1q molecule in solution

Tischenko, V. M.; Zav’yalova, Galina A.; Bliznyukov, O. P.; Zav’yalov, Vladimir P.

doi:10.1016/j.molimm.2003.11.034

Cited by 4 publications

(7 citation statements)

References 76 publications

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“…Our results support the current understanding of the globular domains ghA, ghB and ghC as structurally and functionally independent modules within GHR of C1q [30,31], and allow us to presume the leading role of ghB in the process of binding hydrophobic ligands, affecting and defining the autoantigenicity of the whole C1q molecule. Our results support the current understanding of the globular domains ghA, ghB and ghC as structurally and functionally independent modules within GHR of C1q [30,31], and allow us to presume the leading role of ghB in the process of binding hydrophobic ligands, affecting and defining the autoantigenicity of the whole C1q molecule.…”

Section: Resultssupporting

confidence: 86%

“…The three globular domains were affected by PZ in a different way and each of them exhibited a particular structural contribution to C1q autoantigenicity. Our results support the current understanding of the globular domains ghA, ghB and ghC as structurally and functionally independent modules within GHR of C1q, 30,31 and allow us to presume the leading role of ghB in the process of binding hydrophobic ligands, affecting and defining the autoantigenicity of the whole C1q molecule.…”

Section: Discussionsupporting

confidence: 86%

“…The Trp spectrum of C1q was characterized by a broad spectrum and the registered emission maximum position at 345 nm showed the role of Class II fluorophores, located in a polar microenvironment, similar to previous finding by Tischenko et al, 2004. 31 Our results demonstrated that titration of the native C1q with PZ was accompanied by an increase of Trp emission upon ligand binding. Also, we observed a blue-shift of 7 nm in the emission maximum position which revealed conformational rearrangements within C1q, induced by the ligand PZ.…”

Section: Fluorescence Spectroscopy Of C1q Gha Ghb and Ghc In The Pres...supporting

confidence: 54%

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Autoantigenicity of human C1q is associated with increased hydrophobicity due to conformational transitions in the globular heads

et al. 2015

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We analyzed the structural features of C1q that underlie its autoantigenicity by means of a model system using the amphiphilic polyzwitterion (PZ), poly(ethylene oxide-b-N,N-dimethyl(methacryloyloxyethyl) ammonium propanesulfonate) in the process of C1q immobilization. The source of anti-C1q autoantibodies was human sera from patients with Lupus Nephritis (LN). Both analyzed concentrations of PZ, 25 mM and 50 mM, were found to be applicable for inducing conformational transitions which resulted in increased recognition of C1q and the globular domain of its B polypeptide chain, designated ghB, by the LN autoantibodies. The registered conformational transitions displayed a hydrophobic enhancement of the protein microenvironment due to the presence of hydrophobic binding sites in ghB which consequently affected the autoantigenicity of the whole C1q molecule.

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Section: Resultssupporting

confidence: 86%

Section: Discussionsupporting

confidence: 86%

Section: Fluorescence Spectroscopy Of C1q Gha Ghb and Ghc In The Pres...supporting

confidence: 54%

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Autoantigenicity of human C1q is associated with increased hydrophobicity due to conformational transitions in the globular heads

et al. 2015

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“…The most favoured inhibitor-binding site involves Lys C170 , a residue that has been shown to be important for C1q binding to IgG1, CRP and PTX3 . There are also additional highly probable binding sites, located near residues Lys A200 , Trp A147 , Arg B101 and Arg B108 , which have been shown to be important for C1q target binding (Gaboriaud et al, 2003;Tischenko et al, 2004;Tissot et al, 2005;Zlatarova et al, 2006). Separate docking experiments, performed on isolated A, B and C chains, demonstrated that the B2S binds to practically the same sites on the gC1q and on its isolated chains (Table 2).…”

Section: Discussionmentioning

confidence: 97%

Complement C1q‐target proteins recognition is inhibited by electric moment effectors

Roumenina

Bureeva

Kantardjiev

et al. 2007

J of Molecular Recognition

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Classical complement pathway is an important innate immune mechanism, which is usually triggered by binding of C1q to immunoglobulins, pentraxins and other target molecules. Although the activation of the classical pathway is crucial in the host defence, its undesirable and uncontrolled activation can lead to tissue damage. Thus, understanding the molecular basis of complement activation and its inhibition are of great biomedical importance. Recently, we proposed a mechanism for target recognition and classical pathway activation by C1q, which is likely governed by calcium-controlled reorientation of macromolecular electric moment vectors. Here we sought to define the mechanism of C1q inhibition by low molecular weight disulphate compounds that bind to the globular (gC1q) domain, using experimental, computational docking and theoretical modelling approaches. Our experimental results demonstrate that betulin disulphate (B2S) and 9,9-bis(4'-hydroxyphenyl)fluorene disulphate (F2S) inhibit the interaction of C1q and its recombinant globular modules with target molecules IgG1, C-reactive protein (CRP) and long pentraxin 3 (PTX3). In most C1q-inhibitor docked complexes, there is a reduction of electric moment scalar values and similarly altered direction of electric/dipole moment vectors. This could explain the inhibitory effect by impaired electrostatic steering, lacking optimal target recognition and formation of functional complex. In the presence of the inhibitor, the tilt of gC1q domains is likely to be blocked by the altered direction of the electric moment vector. Thus, the transition from the inactive (closed) towards the active (open) conformation of C1q (i.e. the complement activation signal transmission) will be impaired and the cascade initiation disrupted. These results could serve as a starting point for the exploration of a new form of 'electric moment inhibitors/effectors'.

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“…Support for this hypothesis was recently provided by the revealed crystal structure of C1q. In the postulated C1q-model several hydrophobic amino acid residues are supposed to take part in ligand-recognition and binding (9), which is also reported from Tischenko et al (10). Hydrophobic interactions are supposed to be important in the immune system.…”

mentioning

confidence: 64%

Registration of the Interaction Between C1q Human Complement Derivatives and Immunoglobulins by Elisa—Role of the Solid Phase

Zlatarova

Roumenina

Tsacheva

et al. 2004

Biotechnology & Biotechnological Equipment

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The interaction of C1q, the first subcomponent of the human complement, with its immunoglobulin ligands from immune complexes is the crucial step in the activation of the classical complement pathway. Thus the mechanism of these interaction and the factors, which influence them, are from high interest. In the present study the effect of immobilization of the interacting proteins on a solid support in ELISA was investigated. The obtained results lead us to the conclusion, that the immobilization process may have a significant influence on the binding activity of tested proteins, especially when hydrophobic interactions are involved.

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Thermodynamic, conformational and functional properties of the human C1q globular heads in the intact C1q molecule in solution

Cited by 4 publications

References 76 publications

Autoantigenicity of human C1q is associated with increased hydrophobicity due to conformational transitions in the globular heads

Autoantigenicity of human C1q is associated with increased hydrophobicity due to conformational transitions in the globular heads

Complement C1q‐target proteins recognition is inhibited by electric moment effectors

Registration of the Interaction Between C1q Human Complement Derivatives and Immunoglobulins by Elisa—Role of the Solid Phase

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