Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8

Jianyun Nie, Chao Xu, Jing Jin, Juliette A. Aka, Wolfram Tempel, Vivian Nguyen, Linya You, Ryan Weist, Jinrong Min*, Tony Pawson, Xiang Jiao Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Peptide motifs are often used for protein-protein interactions. We have recently demonstrated that ankyrin repeats of ANKRA2 and the paralogous bare lymphocyte syndrome transcription factor RFXANK recognize PxLPxL/I motifs shared by megalin, three histone deacetylases, and RFX5. We show here that that CCDC8 is a major partner of ANKRA2 but not RFXANK in cells. The CCDC8 gene is mutated in 3M syndrome, a short-stature disorder with additional facial and skeletal abnormalities. Two other genes mutated in this syndrome encode CUL7 and OBSL1. While CUL7 is a ubiquitin ligase and OBSL1 associates with the cytoskeleton, little is known about CCDC8. Binding and structural analyses reveal that the ankyrin repeats of ANKRA2 recognize a PxLPxL motif at the C-terminal region of CCDC8. The N-terminal part interacts with OBSL1 to form a CUL7 ligase complex. These results link ANKRA2 unexpectedly to 3M syndrome and suggest novel regulatory mechanisms for histone deacetylases and RFX7.

Original languageEnglish (US)
Pages (from-to)700-712
Number of pages13
Issue number4
StatePublished - Apr 7 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology


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