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Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase
- Source :
- eLife, Vol 8 (2019)
- Publication Year :
- 2019
- Publisher :
- eLife Sciences Publications Ltd, 2019.
-
Abstract
- The lipid distribution of plasma membranes of eukaryotic cells is asymmetric and phospholipid scramblases disrupt this asymmetry by mediating the rapid, nonselective transport of lipids down their concentration gradients. As a result, phosphatidylserine is exposed to the outer leaflet of membrane, an important step in extracellular signaling networks controlling processes such as apoptosis, blood coagulation, membrane fusion and repair. Several TMEM16 family members have been identified as Ca2+-activated scramblases, but the mechanisms underlying their Ca2+-dependent gating and their effects on the surrounding lipid bilayer remain poorly understood. Here, we describe three high-resolution cryo-electron microscopy structures of a fungal scramblase from Aspergillus fumigatus, afTMEM16, reconstituted in lipid nanodiscs. These structures reveal that Ca2+-dependent activation of the scramblase entails global rearrangement of the transmembrane and cytosolic domains. These structures, together with functional experiments, suggest that activation of the protein thins the membrane near the transport pathway to facilitate rapid transbilayer lipid movement.
- Subjects :
- Phospholipid scramblase
QH301-705.5
Science
Phospholipid
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
membrane structure
Biology (General)
Lipid bilayer
Lipid Transport
phospholipids
030304 developmental biology
0303 health sciences
General Immunology and Microbiology
Chemistry
General Neuroscience
Membrane structure
Lipid bilayer fusion
General Medicine
Phosphatidylserine
Transmembrane protein
Scrambling
membrane channels
Biophysics
Medicine
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....afda0300cfa70bd0e958df911cb6dc80