4rly
From Proteopedia
Crystal Structure of AnkB Ankyrin Repeats (R1-R9) in Complex with Nav1.2 Ankyrin Binding Domain
Structural highlights
DiseaseSCN2A_HUMAN Defects in SCN2A are the cause of seizures, benign familial infantile type 3 (BFIS3) [MIM:607745. An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.[1] [2] [3] [4] Defects in SCN2A are the cause of epileptic encephalopathy early infantile type 11 (EIEE11) [MIM:613721. EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.[5] [6] ANK2_HUMAN Romano-Ward syndrome. Long QT syndrome 4 (LQT4) [MIM:600919: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 4 shows many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature. Note=The disease is caused by mutations affecting the gene represented in this entry.[7] [8] FunctionSCN2A_HUMAN Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.ANK2_HUMAN In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions (By similarity). Attaches integral membrane proteins to cytoskeletal elements. Also binds to cytoskeletal proteins. Required for coordinate assembly of Na/Ca exchanger, Na/K ATPase and InsP3 receptor at sarcoplasmic reticulum sites in cardiomyocytes. Required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) in the inner segment of rod photoreceptors. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate.[9] Publication Abstract from PubMedAnkyrin adaptors together with their spectrin partners coordinate diverse ion channels and cell adhesion molecules within plasma membrane domains and thereby promote physiological activities including fast signaling in the heart and nervous system. Ankyrins specifically bind to numerous membrane targets through their 24 ankyrin repeats (ANK repeats), although the mechanism for the facile and independent evolution of these interactions has not been resolved. Here we report the structures of ANK repeats in complex with an inhibitory segment from the C-terminal regulatory domain and with a sodium channel Nav1.2 peptide, respectively, showing that the extended, extremely conserved inner groove spanning the entire ANK repeat solenoid contains multiple target binding sites capable of accommodating target proteins with very diverse sequences via combinatorial usage of these sites. These structures establish a framework for understanding the evolution of ankyrins' membrane targets, with implications for other proteins containing extended ANK repeat domains. Structural basis of diverse membrane target recognitions by ankyrins.,Wang C, Wei Z, Chen K, Ye F, Yu C, Bennett V, Zhang M Elife. 2014 Nov 10;3. doi: 10.7554/eLife.04353. PMID:25383926[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
Categories: Homo sapiens | Large Structures | Mus musculus | Wang C | Wei Z | Zhang M
