ArticleProceedings of the National Academy of Sciences of the United States of America2016
Atomistic insight into lipid translocation by a TMEM16 scramblase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 125 citations in OpenAlex.
- Structural insight into sodium-dependent bile acid transport by members of the SLC10 family.Structure (London, England : 1993) · 2026Article
- Hydrophobic mismatch induces lipid sorting based on tail unsaturation.bioRxiv : the preprint server for biology · 2026Article
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- Dynamic metabolic modelling of ATP allocation during viral infection.Journal of the Royal Society, Interface · 2026Article
- Conformational changes upon pore blocker removal reveal conductive states of TMEM16A.bioRxiv : the preprint server for biology · 2026Article
- Mechanism of Phosphatidylserine Lipid Scrambling by Human SERINC3, an HIV-1 Restriction Factor.bioRxiv : the preprint server for biology · 2025Article
- Structural basis for lipid transport at membrane contact sites by the IST2-OSH6 complex.Nature structural & molecular biology · 2025Article
- Structure and function of the human apoptotic scramblase Xkr4.Nature communications · 2025Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.eLife · 2025Article
- Article
- Groove architecture controls lipid scrambling in simulations of protein and model systems.bioRxiv : the preprint server for biology · 2025Article
- Shaping the composition of the mitochondrial outer membrane.Nature cell biology · 2025Review
- Lipid Scrambling Pathways in the Sec61 Translocon Complex.Journal of the American Chemical Society · 2025Article
- Simulation-based survey of TMEM16 family reveals that robust lipid scrambling requires an open groove.bioRxiv : the preprint server for biology · 2025Article
- Wide-ranging cellular functions of ion channels and lipid scramblases in the structurally related TMC, TMEM16 and TMEM63 families.Nature structural & molecular biology · 2025Review
- Structural basis of closed groove scrambling by a TMEM16 protein.Nature structural & molecular biology · 2024Article
- Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A.eLife · 2024Article
- In or out of the groove? Mechanisms of lipid scrambling by TMEM16 proteins.Cell calcium · 2024Review
- Lipid scrambling is a general feature of protein insertases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The transmembrane protein 16 (TMEM16) family of membrane proteins includes both lipid scramblases and ion channels involved in olfaction, nociception, and blood coagulation. The crystal structure of the fungal Nectria haematococca TMEM16 (nhTMEM16) scramblase suggested a putative mechanism of lipid transport, whereby polar and charged lipid headgroups move through the low-dielectric environment of the membrane by traversing a hydrophilic groove on the membrane-spanning surface of the protein. Here, we use computational methods to explore the membrane-protein interactions involved in lipid scrambling. Fast, continuum membrane-bending calculations reveal a global pattern of charged and hydrophobic surface residues that bends the membrane in a large-amplitude sinusoidal wave, resulting in bilayer thinning across the hydrophilic groove. Atomic simulations uncover two lipid headgroup-interaction sites flanking the groove. The cytoplasmic site nucleates headgroup-dipole stacking interactions that form a chain of lipid molecules that penetrate into the groove. In two instances, a cytoplasmic lipid interdigitates into this chain, crosses the bilayer, and enters the extracellular leaflet, and the reverse process happens twice as well. Continuum membrane-bending analysis carried out on homology models of mammalian homologs shows that these family members also bend the membrane-even those that lack scramblase activity. Sequence alignments show that the lipid-interaction sites are conserved in many family members but less so in those with reduced scrambling ability. Our analysis provides insight into how large-scale membrane bending and protein chemistry facilitate lipid permeation in the TMEM16 family, and we hypothesize that membrane interactions also affect ion permeation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.