Structural highlights
Disease
[CLCKA_HUMAN] Defects in CLCNKA are a cause of Bartter syndrome type 4B (BS4B) [MIM:613090]. A digenic, recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. Bartter syndrome type 4B is associated with sensorineural deafness.[1] [2]
Function
[CLCKA_HUMAN] Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms.
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 PubMed
The cytoplasmic domains of ClC chloride channels and transporters are ubiquitously found in eukaryotic family members and have been suggested to be involved in the regulation of ion transport. All cytoplasmic ClC domains share a conserved scaffold that contains a pair of CBS motifs. Here we describe the structure of the cytoplasmic component of the human chloride channel ClC-Ka at 1.6 A resolution. The structure reveals a dimeric organization of the domain that is unusual for CBS motif containing proteins. Using a biochemical approach combining mutagenesis, crosslinking, and analytical ultracentrifugation, we demonstrate that the interaction interface is preserved in solution and that the distantly related channel ClC-0 likely exhibits a similar structural organization. Our results reveal a conserved interaction interface that relates the cytoplasmic domains of ClC proteins and establish a structural relationship that is likely general for this important family of transport proteins.
The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface.,Markovic S, Dutzler R Structure. 2007 Jun;15(6):715-25. PMID:17562318[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nozu K, Inagaki T, Fu XJ, Nozu Y, Kaito H, Kanda K, Sekine T, Igarashi T, Nakanishi K, Yoshikawa N, Iijima K, Matsuo M. Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness. J Med Genet. 2008 Mar;45(3):182-6. doi: 10.1136/jmg.2007.052944. PMID:18310267 doi:10.1136/jmg.2007.052944
- ↑ Schlingmann KP, Konrad M, Jeck N, Waldegger P, Reinalter SC, Holder M, Seyberth HW, Waldegger S. Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med. 2004 Mar 25;350(13):1314-9. PMID:15044642 doi:10.1056/NEJMoa032843
- ↑ Markovic S, Dutzler R. The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface. Structure. 2007 Jun;15(6):715-25. PMID:17562318 doi:http://dx.doi.org/10.1016/j.str.2007.04.013
