| 1. |
- Hellmich, Ute A., et al.
(författare)
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TRP channels : branching out into the fungal kingdom
- 2022
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 30:1, s. 2-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- TRP channels have been heavily pursued as cryo-electron microscopy targets since they rang in the "resolution revolution."Although widespread in eukaryotes, a fungal TRP channel structure was missing. In this issue of Structure, Ahmed et al. (2022) present structural insights into the regulation of yeast TRPY1 by Ca2+ and lipids.
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| 2. |
- Howard, Rebecca J., et al.
(författare)
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Permeating disciplines : Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport
- 2018
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : ELSEVIER SCIENCE BV. - 0005-2736 .- 1879-2642. ; 1860:4, s. 927-942
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Forskningsöversikt (refereegranskat)abstract
- Ion translocation across biological barriers is a fundamental requirement for life. In many cases, controlling this process for example with neuroactive drugs demands an understanding of rapid and reversible structural changes in membrane-embedded proteins, including ion channels and transporters. Classical approaches to electrophysiology and structural biology have provided valuable insights into several such proteins over macroscopic, often discontinuous scales of space and time. Integrating these observations into meaningful mechanistic models now relies increasingly on computational methods, particularly molecular dynamics simulations, while surfacing important challenges in data management and conceptual alignment. Here, we seek to provide contemporary context, concrete examples, and a look to the future for bridging disciplinary gaps in biological ion transport. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin Mcllwain.
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| 3. |
- Zhang, Liying, et al.
(författare)
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Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Δ9-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from rat and human mast cells. Each ligand causes distinct conformational changes in TRPV2 as revealed by cryo-EM. Although the binding for probenecid remains elusive, C16 associates within the vanilloid pocket. As such, the C16 binding location is distinct from that of cannabidiol, partially overlapping with the binding site of the TRPV2 inhibitor piperlongumine. Taken together, we discover a new cannabinoid binding site in TRPV2 that is under the influence of allosteric control by probenecid. This molecular insight into ligand modulation enhances our understanding of TRPV2 in normal and pathophysiology.
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