4LG6

Crystal structure of ANKRA2-CCDC8 complex

Summary for 4LG6

• Entry DOI: 10.2210/pdb4lg6/pdb
• Descriptor: Ankyrin repeat family A protein 2, Coiled-coil domain-containing protein 8, UNKNOWN ATOM OR ION, ... (4 entities in total)
• Functional Keywords: structural genomics consortium, sgc, ankyrin repeat, structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton : Q9H9E1; Cytoplasm : Q9H0W5
• Total number of polymer chains: 2
• Total formula weight: 20861.77

Authors

Xu, C.,Bian, C.,Tempel, W.,Mackenzie, F.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2013-06-27, release date: 2013-09-25, Last modification date: 2023-09-20)

Primary citation

Nie, J.,Xu, C.,Jin, J.,Aka, J.A.,Tempel, W.,Nguyen, V.,You, L.,Weist, R.,Min, J.,Pawson, T.,Yang, X.J.
Ankyrin Repeats of ANKRA2 Recognize a PxLPxL Motif on the 3M Syndrome Protein CCDC8.
Structure, 23:700-712, 2015

PubMed Abstract: 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.

PubMed: 25752541
DOI: 10.1016/j.str.2015.02.001

Experimental method

X-RAY DIFFRACTION (1.8 Å)