4WIT

TMEM16 lipid scramblase in crystal form 2

Summary for 4WIT

• Entry DOI: 10.2210/pdb4wit/pdb
• Related: 4WIS
• Descriptor: Predicted protein, CALCIUM ION (2 entities in total)
• Functional Keywords: membrane protein, calcium activation, transport protein, lipid transport
• Biological source: Nectria haematococca
• Total number of polymer chains: 2
• Total formula weight: 166560.33

Authors

Dutzler, R.,Brunner, J.D.,Lim, N.K.,Schenck, S. (deposition date: 2014-09-26, release date: 2014-11-12, Last modification date: 2024-05-08)

Primary citation

Brunner, J.D.,Lim, N.K.,Schenck, S.,Duerst, A.,Dutzler, R.
X-ray structure of a calcium-activated TMEM16 lipid scramblase.
Nature, 516:207-212, 2014

PubMed Abstract: 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.

PubMed: 25383531
DOI: 10.1038/nature13984

Experimental method

X-RAY DIFFRACTION (3.4 Å)