Role of Structure-Based Changes due to Somatic Mutation in Highly Homologous DNA-Binding and DNA-Hydrolyzing Autoantibodies Exemplified by A23P Substitution in the VH Domain
Joint Authors
Gabibov, A. G.
Bogun, A. G.
Khlyntseva, A. E.
Shemyakin, I. G.
Savchenko, G. A.
Kolesnikov, A. V.
Kozyr, A. V.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-11-11
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Anti-DNA autoantibodies are responsible for tissue injury in lupus.
A subset of DNA-specific antibodies capable of DNA cleavage can be even more harmful after entering the living cells by destroying nuclear DNA.
Origins of anti-DNA autoantibodies are not fully understood, and the mechanism of induction of DNA-cleaving activity remains speculative.
The autoantibody BV04-01 derived from lupus-prone mouse is the only DNA-hydrolyzing immunoglobulin with known 3D structure.
Identification and analysis of antibodies homologous to BV04-01 may help to understand molecular bases and origins of DNA-cleaving activity of autoantibodies.
BLAST search identified murine anti-DNA autoantibody MRL-4 with sequences of variable region genes highly homologous to those of autoantibody BV04-01.
Despite significant homology to BV04-01, not only MRL-4 had no DNA-cleaving activity, but also reversion of its unusual P23 mutation to the germline alanine resulted in a dramatic loss of affinity to DNA.
Contrary to this effect, transfer of the P23 mutation to the BV04-01 has resulted in a significant drop in DNA binding and almost complete loss of catalytic activity.
In the present paper we analyzed the properties of two homologous autoantibodies and mutants thereof and discussed the implications of unusual somatic mutations for the development of autoantibodies with DNA-binding and DNA-hydrolyzing activity.
American Psychological Association (APA)
Kozyr, A. V.& Kolesnikov, A. V.& Khlyntseva, A. E.& Bogun, A. G.& Savchenko, G. A.& Shemyakin, I. G.…[et al.]. 2012. Role of Structure-Based Changes due to Somatic Mutation in Highly Homologous DNA-Binding and DNA-Hydrolyzing Autoantibodies Exemplified by A23P Substitution in the VH Domain. Autoimmune Diseases،Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-490284
Modern Language Association (MLA)
Kozyr, A. V.…[et al.]. Role of Structure-Based Changes due to Somatic Mutation in Highly Homologous DNA-Binding and DNA-Hydrolyzing Autoantibodies Exemplified by A23P Substitution in the VH Domain. Autoimmune Diseases No. 2012 (2012), pp.1-7.
https://search.emarefa.net/detail/BIM-490284
American Medical Association (AMA)
Kozyr, A. V.& Kolesnikov, A. V.& Khlyntseva, A. E.& Bogun, A. G.& Savchenko, G. A.& Shemyakin, I. G.…[et al.]. Role of Structure-Based Changes due to Somatic Mutation in Highly Homologous DNA-Binding and DNA-Hydrolyzing Autoantibodies Exemplified by A23P Substitution in the VH Domain. Autoimmune Diseases. 2012. Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-490284
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-490284