Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies...

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Bibliographic Details
Published in:Molecular biology (New York) 2016-05, Vol.50 (3), p.442-451
Main Authors: Akberova, N. I., Zhmurov, A. A., Nevzorova, T. A., Litvinov, R. I.
Format: Article
Language:English
Subjects:
Autoimmune diseases
Biochemistry
Biomedical and Life Sciences
Deoxyribonucleic acid
DNA
Human Genetics
Life Sciences
Molecular biology
Pathogenesis
Structural and Functional Analysis of Biopolymers and Their Complexes
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Summary:Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibodydsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893316020023