2d46
From Proteopedia
Solution Structure of the Human Beta4a-A Domain
Structural highlights
Disease[CACB4_HUMAN] Defects in CACNB4 are the cause of susceptibility to epilepsy, idiopathic generalized type 9 (EIG9) [MIM:607682]. A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.[1] Defects in CACNB4 are the cause of susceptibility to juvenile myoclonic epilepsy type 6 (EJM6) [MIM:607682]. EJM6 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Defects in CACNB4 are the cause of episodic ataxia type 5 (EA5) [MIM:613855]. EA5 is a disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.[2] Function[CACB4_HUMAN] The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCa2+ channel beta subunits regulate trafficking and gating (opening and closing) of voltage-dependent Ca2+ channel alpha1 subunits. Based on primary sequence comparisons, they are thought to be modular structures composed of five domains (A-E) that are related to the large family of membrane associated guanylate-kinase (MAGUK) proteins. The crystal structures of the beta subunit core, B-D, domains have recently been reported; however, very little is known about the structures of the A and E domains. The N-terminal A domain is a hypervariable region that differs among the four subtypes of Ca2+ channel beta subunits (beta1-beta4). Furthermore, this domain undergoes alternative splicing to create multiple N-terminal structures within a given gene class that have distinct effects on gating. We have solved the solution structure of the A domain of the human beta4a subunit, a splice variant that we have shown previously to have alpha1 subunit subtype-specific effects on Ca2+ channel trafficking and gating. Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit.,Vendel AC, Rithner CD, Lyons BA, Horne WA Protein Sci. 2006 Feb;15(2):378-83. Epub 2005 Dec 29. PMID:16385006[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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