𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Effect of somatic mutation on DNA binding properties of anti-DNA autoantibodies

✍ Scribed by Melissa J. Bobeck; Joanne Cleary; Jenny A. Beckingham; P. Christine Ackroyd; Gary D. Glick

Publisher
Wiley (John Wiley & Sons)
Year
2007
Tongue
English
Weight
175 KB
Volume
85
Category
Article
ISSN
0006-3525

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Autoantibodies that bind DNA are a hallmark of systemic lupus erythematosus. A subset of autoantibody•DNA complexes localize to kidney tissue and lead to damage and even death. 11F8, 9F11, and 15B10 are clonally related anti‐DNA autoantibodies isolated from an autoimmune mouse. 11F8 binds ssDNA in a sequence‐specific manner and causes tissue damage, while 9F11 and 15B10 bind ssDNA non‐specifically and are benign. Among these antibodies, DNA binding properties are mediated by five amino acid differences in primary sequence. Thermodynamic and kinetic parameters associated with recognition of structurally different DNA sequences were determined for each antibody to provide insight toward recognition strategies, and to explore a link between binding properties and disease pathogenesis. A model of 11F8 bound to its high affinity consensus sequence provides a foundation for understanding the differences in thermodynamic and kinetic parameters between the three mAbs. Our data suggest that 11F8 utilizes the proposed ssDNA recognition motif including ^Y32^V~L~, a hydrogen bonding residue at ^91^V~L~, and an aromatic residue at the tip of the third heavy chain complementarity determining region. Interestingly, a somatic mutation to arginine at ^31^V~H~ in 11F8 may afford additional binding site contacts including ^R31^V~H~, ^R96^V~H~, and ^R98^V~H~ that could determine specificity. © 2007 Wiley Periodicals, Inc. Biopolymers 85: 471–480, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]

📜 SIMILAR VOLUMES

Binding of human anti-DNA autoantibodies
Binding of human anti-DNA autoantibodies to reactive oxygen species modified-DNA and probing oxidative DNA damage in cancer using monoclonal antibody
✍ Badithe T. Ashok; Rashid Ali 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 French ⚖ 96 KB 👁 2 views

The binding of native and reactive oxygen species-modified DNA (ROS-DNA) to circulating antibodies in the serum of patients with various types of cancer has been investigated by competition enzyme-linked immunosorbent assay. Fifteen sera of 35 showed reactivity with native and/or ROS-DNA. Eleven of

Direct binding of anti–DNA topoisomerase
Direct binding of anti–DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis
✍ Jill Hénault; Mélanie Tremblay; Isabelle Clément; Yves Raymond; Jean-Luc Senécal 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 English ⚖ 265 KB 👁 2 views

## Abstract ## Objective Fibroblasts play a crucial role in the development of systemic sclerosis (SSc), and antifibroblast antibodies (AFAs) capable of inducing a proinflammatory phenotype in fibroblasts have been detected in the sera of SSc patients. This study examined the prevalence of AFAs in

Structure-function analysis of a lupus a
Structure-function analysis of a lupus anti-DNA autoantibody: central role of the heavy chain complementarity-determining region 3 Arg in binding of double- and single-stranded DNA
✍ Zongdong Li; Edward W. Schettino; Eduardo A. Padlan; Hideyuki Ikematsu; Paolo Ca 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 255 KB 👁 2 views

To determine the contribution of the somatic point mutations and that of the complementarity-determining region (CDR)3 Arg to DNA binding, we engineered the germline V H and V ‹ gene revertant and site-mutagenized the CDR3 Arg residues of the mutated and "antigen-selected" mAb 412.67. This anti-DNA