Mechanical stability of the antibody domain CH3 homodimer in different oxidation states

Morten Bertz*, Johannes Buchner, Matthias Rief

*この研究の対応する著者

研究成果: Article査読

12 被引用数 (Scopus)

抄録

The CH3 homodimer at the C-terminal end of the antibody heavy chain is the key noncovalent interaction stabilizing antibody proteins. Here, we use single-molecule force spectroscopy to investigate the dissociation mechanics of CH3 as a proxy for antibody mechanical stability. We find the CH3 homodimer to be a highly stable complex, and its dissociation force of >150 pN at a loading rate of ≈5500 pN/s exceeds the stability of most protein-protein interactions studied to date. Separated C H3 monomers, on the other hand, are mechanically labile and only short-lived. Each CH3 monomer contains a conserved buried disulfide bridge, and we find that the successive reduction of one or both disulfide bridges in the dimer results in a stepwise decrease of the dissociation force. This suggests a structural role of the disulfide bridges helping to mold the high-affinity domain-domain interface, even though they are neither required for nor directly involved in dimerization. Taken together, our results set a limit on how much force a single antibody can bear and reveal the CH3 homodimer as a mechanical fastener that prevents antibody dissociation.

本文言語English
ページ(範囲)15085-15091
ページ数7
ジャーナルJournal of the American Chemical Society
135
40
DOI
出版ステータスPublished - 2013 10月 9

ASJC Scopus subject areas

  • 触媒
  • 化学 (全般)
  • 生化学
  • コロイド化学および表面化学

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