Publication Date:
2014-11-11
Description:
The TMEM16 family of proteins, also known as anoctamins, features a remarkable functional diversity. This family contains the long sought-after Ca(2+)-activated chloride channels as well as lipid scramblases and cation channels. Here we present the crystal structure of a TMEM16 family member from the fungus Nectria haematococca that operates as a Ca(2+)-activated lipid scramblase. Each subunit of the homodimeric protein contains ten transmembrane helices and a hydrophilic membrane-traversing cavity that is exposed to the lipid bilayer as a potential site of catalysis. This cavity harbours a conserved Ca(2+)-binding site located within the hydrophobic core of the membrane. Mutations of residues involved in Ca(2+) coordination affect both lipid scrambling in N. haematococca TMEM16 and ion conduction in the Cl(-) channel TMEM16A. The structure reveals the general architecture of the family and its mode of Ca(2+) activation. It also provides insight into potential scrambling mechanisms and serves as a framework to unravel the conduction of ions in certain TMEM16 proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunner, Janine D -- Lim, Novandy K -- Schenck, Stephan -- Duerst, Alessia -- Dutzler, Raimund -- England -- Nature. 2014 Dec 11;516(7530):207-12. doi: 10.1038/nature13984. Epub 2014 Nov 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383531" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Binding Sites/genetics
;
Calcium/chemistry/*metabolism/pharmacology
;
Chloride Channels/*chemistry/genetics/*metabolism
;
Crystallography, X-Ray
;
Electric Conductivity
;
Humans
;
Hydrophobic and Hydrophilic Interactions
;
Ion Transport/drug effects
;
Lipid Bilayers/chemistry/metabolism
;
Models, Molecular
;
Molecular Sequence Data
;
Nectria/*chemistry/enzymology/genetics
;
Neoplasm Proteins/chemistry
;
Phospholipid Transfer Proteins/*chemistry/genetics/*metabolism
;
Protein Multimerization
;
Protein Structure, Secondary
;
Protein Subunits/chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
