4o6x

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Crystal structure of human Ankyrin G death domain

Structural highlights

4o6x is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ANK3_HUMAN Intellectual disability - hypotonia - spasticity - sleep disorder;Schizophrenia. Genetic variations in ANK3 may be associated with autism spectrum disorders susceptibility. The disease is caused by mutations affecting the gene represented in this entry. A homozygous deletion in ANK3 predicted to result in frameshift and premature truncation, has been shown to be the cause of moderate intellectual disability, an ADHD-like phenotype and behavioral problems in a consanguineous family (PubMed:23390136).^[1]

Function

ANK3_HUMAN In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. Isoform 5: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin.

Publication Abstract from PubMed

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 A crystal structure of human AnkG death domain (hAnkG-DD). The core death domain is composed of six alpha-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 alpha6 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.Proteins 2014. (c) 2014 Wiley Periodicals, Inc.

Crystal structure of human Ankyrin G death domain.,Liu Y, Zhang Y, Wang JH Proteins. 2014 Oct 11. doi: 10.1002/prot.24702. PMID:25307106^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Iqbal Z, Vandeweyer G, van der Voet M, Waryah AM, Zahoor MY, Besseling JA, Roca LT, Vulto-van Silfhout AT, Nijhof B, Kramer JM, Van der Aa N, Ansar M, Peeters H, Helsmoortel C, Gilissen C, Vissers LE, Veltman JA, de Brouwer AP, Frank Kooy R, Riazuddin S, Schenck A, van Bokhoven H, Rooms L. Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders. Hum Mol Genet. 2013 May 15;22(10):1960-70. doi: 10.1093/hmg/ddt043. Epub 2013 Feb, 5. PMID:23390136 doi:http://dx.doi.org/10.1093/hmg/ddt043
↑ Liu Y, Zhang Y, Wang JH. Crystal structure of human Ankyrin G death domain. Proteins. 2014 Oct 11. doi: 10.1002/prot.24702. PMID:25307106 doi:http://dx.doi.org/10.1002/prot.24702