14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination

Zhenming Xu, Zsolt Fulop, Guikai Wu, Egest J. Pone, Jinsong Zhang, Thach Mai, Lisa M. Thomas, Ahmed Al-Qahtani, Clayton A. White, Seok Rae Park, Petra Steinacker, Zenggang Li, John Yates, Bruce Herron, Markus Otto, Hong Zan, Haian Fu, Paolo Casali

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Class switch DNA recombination (CSR) is the mechanism that diversifies the biological effector functions of antibodies. Activation-induced cytidine deaminase (AID), a key protein in CSR, targets immunoglobulin H (IgH) switch regions, which contain 5'-AGCT-3' repeats in their core. How AID is recruited to switch regions remains unclear. Here we show that 14-3-3 adaptor proteins have an important role in CSR. 14-3-3 proteins specifically bound 5'-AGCT-3' repeats, were upregulated in B cells undergoing CSR and were recruited with AID to the switch regions that are involved in CSR events (Sμ→Sγ1, Sμ→Sγ3 or Sμ→Sa). Moreover, blocking 14-3-3 by difopein, 14-3-3g deficiency or expression of a dominant-negative 14-3-3α mutant impaired recruitment of AID to switch regions and decreased CSR. Finally, 14-3-3 proteins interacted directly with AID and enhanced AID-mediated in vitro DNA deamination, further emphasizing the important role of these adaptors in CSR.

Original languageEnglish (US)
Pages (from-to)1124-1135
Number of pages12
JournalNature Structural and Molecular Biology
Volume17
Issue number9
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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