title: Crystal structure of human Ankyrin G death domain.
abstract: Ankyrins (Ank) are a ubiquitously expressed family of multifunctional membrane adapter proteins. Ankyrin G (AnkG) is critical for assembling and maintenance of the axon initial segment. Here we present the 2.1 Å crystal structure of human AnkG death domain (hAnkG-DD). The core death domain is composed of six α-helices and three 3₁₀-helices. It forms a hydrophobic pocket on the surface of the molecule. The C-terminal tail of the hAnkG-DD curves back to have the aromatic ring of a phenylalanine residue, Phe100 insert into this pocket, which anchors the flexible tail onto the core domain. Related DDs were selected for structure comparison. The major variations are at the C-terminal region, including the α6 and the long C-terminal extension. The results of size exclusion chromatography and analytical ultracentrifugation suggest that hAnkG-DD exists as monomer in solution. Our work should help for the future investigation of the structure-function of AnkG.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jia-Huai
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry* / Q000235:genetics; D002850:Chromatography, Gel; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D012995:Solubility; D013499:Surface Properties; D014461:Ultracentrifugation
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010649:Phenylalanine
keywords: 310-helix; apoptosis; axon initial segment; hydrophobic pocket; monomer