View source for 7qet


==human Connexin 26 dodecamer at 20mmHg PCO2, pH7.4==
<StructureSection load='7qet' size='340' side='right'caption='[[7qet]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qet]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QET FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=PTY:PHOSPHATIDYLETHANOLAMINE'>PTY</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qet OCA], [https://pdbe.org/7qet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qet RCSB], [https://www.ebi.ac.uk/pdbsum/7qet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qet ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/CXB2_HUMAN CXB2_HUMAN]] KID syndrome;Knuckle pads - leuconychia - sensorineural deafness;Autosomal dominant nonsyndromic sensorineural deafness type DFNA;Autosomal recessive nonsyndromic sensorineural deafness type DFNB;Palmoplantar keratoderma - deafness;Keratoderma hereditarium mutilans. Defects in GJB2 are the cause of deafness autosomal recessive type 1A (DFNB1A) [MIM:[https://omim.org/entry/220290 220290]]. DFNB1A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:11439000</ref> <ref>PMID:14722929</ref> <ref>PMID:15666300</ref> <ref>PMID:15994881</ref> <ref>PMID:9328482</ref> <ref>PMID:9336442</ref> <ref>PMID:9529365</ref> <ref>PMID:9471561</ref> <ref>PMID:10830906</ref> <ref>PMID:11313763</ref> <ref>PMID:12239718</ref> <ref>PMID:12121355</ref> <ref>PMID:12786758</ref> <ref>PMID:15592461</ref> <ref>PMID:17660464</ref> <ref>PMID:19384972</ref>   Defects in GJB2 are the cause of deafness autosomal dominant type 3A (DFNA3A) [MIM:[https://omim.org/entry/601544 601544]].  Defects in GJB2 are a cause of Vohwinkel syndrome (VS) [MIM:[https://omim.org/entry/124500 124500]]. VS is an autosomal dominant disease characterized by hyperkeratosis, constriction on finger and toes and congenital deafness.<ref>PMID:12668604</ref> <ref>PMID:10369869</ref>   Defects in GJB2 are a cause of palmoplantar keratoderma with deafness (PPKDFN) [MIM:[https://omim.org/entry/148350 148350]]. PPKDFN is an autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness.<ref>PMID:12668604</ref> <ref>PMID:9856479</ref> <ref>PMID:10757647</ref> <ref>PMID:10633135</ref> <ref>PMID:12372058</ref> <ref>PMID:15996214</ref> <ref>PMID:17993581</ref>   Defects in GJB2 are a cause of keratitis-ichthyosis-deafness syndrome (KID syndrome) [MIM:[https://omim.org/entry/148210 148210]]; an autosomal dominant form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. KID syndrome is characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails.  Defects in GJB2 are the cause of Bart-Pumphrey syndrome (BPS) [MIM:[https://omim.org/entry/149200 149200]]. BPS is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability.<ref>PMID:15482471</ref> <ref>PMID:15952212</ref>   Defects in GJB2 are the cause of ichthyosis hystrix-like with deafness syndrome (HID syndrome) [MIM:[https://omim.org/entry/602540 602540]]. HID syndrome is an autosomal-dominant inherited keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis. 
== Function ==
[[https://www.uniprot.org/uniprot/CXB2_HUMAN CXB2_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. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Connexins form large-pore channels that function either as dodecameric gap junctions or hexameric hemichannels to allow the regulated movement of small molecules and ions across cell membranes. Opening or closing of the channels is controlled by a variety of stimuli, and dysregulation leads to multiple diseases. An increase in the partial pressure of carbon dioxide (PCO2) has been shown to cause connexin26 (Cx26) gap junctions to close. Here, we use cryoelectron microscopy (cryo-EM) to determine the structure of human Cx26 gap junctions under increasing levels of PCO2. We show a correlation between the level of PCO2 and the size of the aperture of the pore, governed by the N-terminal helices that line the pore. This indicates that CO2 alone is sufficient to cause conformational changes in the protein. Analysis of the conformational states shows that movements at the N terminus are linked to both subunit rotation and flexing of the transmembrane helices.

Conformational changes and CO2-induced channel gating in connexin26.,Brotherton DH, Savva CG, Ragan TJ, Dale N, Cameron AD Structure. 2022 Mar 3. pii: S0969-2126(22)00046-6. doi:, 10.1016/j.str.2022.02.010. PMID:35276081<ref>PMID:35276081</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qet" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Brotherton, D H]]
[[Category: Cameron, A D]]
[[Category: Ragan, T J]]
[[Category: Savva, C G]]
[[Category: Carbon dioxide sensitive]]
[[Category: Gap junction]]
[[Category: Ion channel]]
[[Category: Membrane protein]]