View source for 5era


==Human Connexin-26 (Calcium-free)==
<StructureSection load='5era' size='340' side='right'caption='[[5era]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5era]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ERA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ERA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.8&#8491;</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=5era FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5era OCA], [https://pdbe.org/5era PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5era RCSB], [https://www.ebi.ac.uk/pdbsum/5era PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5era 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.
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== Publication Abstract from PubMed ==
Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca(2+) blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca(2+). The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca(2+) coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca(2+)chelation. Computational analysis revealed that Ca(2+)-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K(+) into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore.

An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.,Bennett BC, Purdy MD, Baker KA, Acharya C, McIntire WE, Stevens RC, Zhang Q, Harris AL, Abagyan R, Yeager M Nat Commun. 2016 Jan 12;7:8770. doi: 10.1038/ncomms9770. PMID:26753910<ref>PMID:26753910</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5era" style="background-color:#fffaf0;"></div>

==See Also==
*[[Connexin 3D structure|Connexin 3D structure]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker KA]]
[[Category: Bennett BC]]
[[Category: Purdy MD]]
[[Category: Yeager MJ]]