| Structural highlights
Function
[ANO1_MOUSE] Calcium-activated chloride channel (CaCC) which plays an important role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The calcium-activated chloride channel TMEM16A is a member of a conserved protein family that comprises ion channels and lipid scramblases. Although the structure of the scramblase nhTMEM16 has defined the architecture of the family, it was unknown how a channel has adapted to cope with its distinct functional properties. Here we have addressed this question by the structure determination of mouse TMEM16A by cryo-electron microscopy and a complementary functional characterization. The protein shows a similar organization to nhTMEM16, except for changes at the site of catalysis. There, the conformation of transmembrane helices constituting a membrane-spanning furrow that provides a path for lipids in scramblases has changed to form an enclosed aqueous pore that is largely shielded from the membrane. Our study thus reveals the structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the diverse functional behavior in the TMEM16 family.
Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A.,Paulino C, Neldner Y, Lam AK, Kalienkova V, Brunner JD, Schenck S, Dutzler R Elife. 2017 May 31;6. pii: e26232. doi: 10.7554/eLife.26232. PMID:28561733[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rock JR, Futtner CR, Harfe BD. The transmembrane protein TMEM16A is required for normal development of the murine trachea. Dev Biol. 2008 Sep 1;321(1):141-9. Epub 2008 Jun 14. PMID:18585372 doi:http://dx.doi.org/S0012-1606(08)00997-4
- ↑ Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, Park SP, Lee J, Lee B, Kim BM, Raouf R, Shin YK, Oh U. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature. 2008 Oct 30;455(7217):1210-5. Epub 2008 Aug 24. PMID:18724360 doi:http://dx.doi.org/nature07313
- ↑ Kunzelmann K, Schreiber R, Kmit A, Jantarajit W, Martins JR, Faria D, Kongsuphol P, Ousingsawat J, Tian Y. Expression and function of epithelial anoctamins. Exp Physiol. 2012 Feb;97(2):184-92. doi: 10.1113/expphysiol.2011.058206. Epub, 2011 Sep 9. PMID:21908539 doi:http://dx.doi.org/10.1113/expphysiol.2011.058206
- ↑ Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM. Anoctamins and gastrointestinal smooth muscle excitability. Exp Physiol. 2012 Feb;97(2):200-6. doi: 10.1113/expphysiol.2011.058248. Epub 2011, Oct 14. PMID:22002868 doi:http://dx.doi.org/10.1113/expphysiol.2011.058248
- ↑ Duran C, Qu Z, Osunkoya AO, Cui Y, Hartzell HC. ANOs 3-7 in the anoctamin/Tmem16 Cl- channel family are intracellular proteins. Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C482-93. doi:, 10.1152/ajpcell.00140.2011. Epub 2011 Nov 9. PMID:22075693 doi:http://dx.doi.org/10.1152/ajpcell.00140.2011
- ↑ Paulino C, Neldner Y, Lam AK, Kalienkova V, Brunner JD, Schenck S, Dutzler R. Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A. Elife. 2017 May 31;6. pii: e26232. doi: 10.7554/eLife.26232. PMID:28561733 doi:http://dx.doi.org/10.7554/eLife.26232
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