2MKL

Solution structure of the fourth constant immunoglobulin domain of nurse shark IgNAR

2MKL の概要

• エントリーDOI: 10.2210/pdb2mkl/pdb
• NMR情報: BMRB: 19783
• 分子名称: Novel antigen receptor (1 entity in total)
• 機能のキーワード: ig domain, ignar, immune system
• 由来する生物種: Ginglymostoma cirratum (Nurse shark)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11832.43

構造登録者

Hennig, J.,Sattler, M. (登録日: 2014-02-10, 公開日: 2014-07-02, 最終更新日: 2024-10-09)

主引用文献

Feige, M.J.,Grawert, M.A.,Marcinowski, M.,Hennig, J.,Behnke, J.,Auslander, D.,Herold, E.M.,Peschek, J.,Castro, C.D.,Flajnik, M.,Hendershot, L.M.,Sattler, M.,Groll, M.,Buchner, J.
The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins.
Proc.Natl.Acad.Sci.USA, 111:8155-8160, 2014

PubMed Abstract: Sharks and other cartilaginous fish are the phylogenetically oldest living organisms that rely on antibodies as part of their adaptive immune system. They produce the immunoglobulin new antigen receptor (IgNAR), a homodimeric heavy chain-only antibody, as a major part of their humoral adaptive immune response. Here, we report the atomic resolution structure of the IgNAR constant domains and a structural model of this heavy chain-only antibody. We find that despite low sequence conservation, the basic Ig fold of modern antibodies is already present in the evolutionary ancient shark IgNAR domains, highlighting key structural determinants of the ubiquitous Ig fold. In contrast, structural differences between human and shark antibody domains explain the high stability of several IgNAR domains and allowed us to engineer human antibodies for increased stability and secretion efficiency. We identified two constant domains, C1 and C3, that act as dimerization modules within IgNAR. Together with the individual domain structures and small-angle X-ray scattering, this allowed us to develop a structural model of the complete IgNAR molecule. Its constant region exhibits an elongated shape with flexibility and a characteristic kink in the middle. Despite the lack of a canonical hinge region, the variable domains are spaced appropriately wide for binding to multiple antigens. Thus, the shark IgNAR domains already display the well-known Ig fold, but apart from that, this heavy chain-only antibody employs unique ways for dimerization and positioning of functional modules.

PubMed: 24830426
DOI: 10.1073/pnas.1321502111

実験手法

SOLUTION NMR