5kk9

Connexin 32 G12R N-Terminal Mutant,

spinqualitylabelsall models 5kk9 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5kk9 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: ACE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CXB1_HUMAN X-linked Charcot-Marie-Tooth disease type 1;X-linked progressive cerebellar ataxia. The disease is caused by mutations affecting the gene represented in this entry. The gene represented in this entry may act as a disease modifier. Function CXB1_HUMAN One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Publication Abstract from PubMed Alterations in gap junctions underlie the etiologies of syndromic deafness (KID) and Charcot-Marie Tooth disease (CMTX). Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the N-termini into the channel pore allowing voltage gating. The loss of this turn correlates with loss of Connexin 32 (Cx32) function by impaired trafficking to the cell membrane. Using (1)H NMR we show the N-terminus of a syndromic deafness mutation Cx26G12R, producing "leaky channels", contains a turn around G12 which is less structured and more flexible than wild-type. In contrast, the N-terminal structure of the same mutation in Cx32 chimera, Cx32*43E1G12R shows a larger constricted turn and no membrane current expression but forms membrane inserted hemichannels. Their function was rescued by formation of heteromeric channels with wild type subunits. We suggest the inflexible Cx32G12R N-terminus blocks ion conduction in homomeric channels and this channel block is relieved by incorporation of wild type subunits. In contrast, the increased open probability of Cx26G12R hemichannels is likely due to the addition of positive charge in the channel pore changing pore electrostatics and impairing hemichannel regulation by Ca(2+). These results provide mechanistic information on aberrant channel activity observed in disease. Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using (1)H NMR spectroscopy.,Batir Y, Bargiello TA, Dowd TL Arch Biochem Biophys. 2016 Oct 15;608:8-19. doi: 10.1016/j.abb.2016.06.019. Epub , 2016 Jul 1. PMID:27378082 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Connexin 3D structure

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