scholarly journals Ion currents through Kir potassium channels are gated by anionic lipids

2021 ◽  
Author(s):  
Ruitao Jin ◽  
Sitong He ◽  
Katrina A. Black ◽  
Oliver B. Clarke ◽  
Di Wu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Fatty Acyl ◽  
Lipid Binding ◽  
Ion Currents ◽  
Ion Conduction ◽  
Head Groups ◽  
Conduction Pathway ◽  
Anionic Lipids ◽  
Surface Groove ◽  
Lipid Binding Site

AbstractIon currents through potassium channels are gated. Constriction of the ion conduction pathway at the inner helix bundle, the textbook ‘gate’ of Kir potassium channels, has been shown to be an ineffective permeation control, creating a rift in our understanding of how these channels are gated. Here we present the first evidence that anionic lipids act as interactive response elements sufficient to gate potassium conduction. We demonstrate the limiting barrier to K+ permeation lies within the ion conduction pathway and show that this ‘gate’ is operated by the fatty acyl tails of lipids that infiltrate the conduction pathway via fenestrations in the walls of the pore. Acyl tails occupying a surface groove extending from the cytosolic interface to the conduction pathway provide a potential means of relaying cellular signals, mediated by anionic lipid head groups bound at the canonical lipid binding site, to the internal gate.

scholarly journals The conduction pathway of potassium channels is water free under physiological conditions

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw6756 ◽  
Author(s):  
Carl Öster ◽  
Kitty Hendriks ◽  
Wojciech Kopec ◽  
Veniamin Chevelkov ◽  
Chaowei Shi ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Direct Contact ◽  
Selectivity Filter ◽  
Water Molecules ◽  
Potassium Ions ◽  
Ion Conduction ◽  
Physiological Conditions ◽  
Conduction Pathway ◽  
Fundamental Process ◽  
Dynamics Simulations

Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a “water-mediated” knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a “direct” knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism.

scholarly journals High-affinity binding of very-long-chain fatty acyl-CoA esters to the peroxisomal non-specific lipid-transfer protein (sterol carrier protein-2)

1999 ◽  
Vol 339 (1) ◽  
pp. 193-199 ◽  
Author(s):  
Tobias B. DANSEN ◽  
Jan WESTERMAN ◽  
Fred S. WOUTERS ◽  
Ronald J. A. WANDERS ◽  
Arie van HOEK ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Lipid Transfer Protein ◽  
Fatty Acyl ◽  
Lipid Binding ◽  
Tryptophan Residue ◽  
Lipid Transfer ◽  
Transfer Protein ◽  
Specific Lipid ◽  
Long Chain ◽  
Lipid Binding Site

Binding of fluorescent fatty acids to bovine liver non-specific lipid-transfer protein (nsL-TP) was assessed by measuring fluorescence resonance energy transfer (FRET) between the single tryptophan residue of nsL-TP and the fluorophore. Upon addition of pyrene dodecanoic acid (Pyr-C12) and cis-parinaric acid to nsL-TP, FRET was observed indicating that these fatty acids were accommodated in the lipid binding site closely positioned to the tryptophan residue. Substantial binding was observed only when these fatty acids were presented in the monomeric form complexed to β-cyclodextrin. As shown by time-resolved fluorescence measurements, translocation of Pyr-C12 from the Pyr-C12–β-cyclodextrin complex to nsL-TP changed dramatically the direct molecular environment of the pyrene moiety: i.e. the fluorescence lifetime of the directly excited pyrene increased at least by 25% and a distinct rotational correlation time of 7 ns was observed. In order to evaluate the affinity of nsL-TP for intermediates of the β-oxidation pathway, a binding assay was developed based on the ability of fatty acyl derivatives to displace Pyr-C12 from the lipid binding site as reflected by the reduction of FRET. Hexadecanoyl-CoA and 2-hexadecenoyl-CoA were found to bind readily to nsL-TP, whereas 3-hydroxyhexadecanoyl-CoA and 3-ketohexadecanoyl-CoA bound poorly. The highest affinities were observed for the very-long-chain fatty acyl-CoA esters (24:0-CoA, 26:0-CoA) and their enoyl derivatives (24:1-CoA, 26:1-CoA). Binding of non-esterified hexadecanoic acid and tetracosanoic acid (24:0) was negligible.

Microstructural morphology of sphingolipid dispersions as investigated by freeze-fracture EM

1995 ◽  
Vol 53 ◽  
pp. 944-945
Author(s):  
Vitthal S. Kulkarni ◽  
Wayne H. Anderson ◽  
Rhoderick E. Brown
Keyword(s):  
Acyl Chain ◽  
Biological Significance ◽  
Freeze Fracture ◽  
Fatty Acyl ◽  
Fatty Acyl Moiety ◽  
Aqueous Dispersions ◽  
Head Groups ◽  
Lipid Species ◽  
Microstructural Morphology ◽  
Layer Chromatography

The biological significance of the sphingomyelins (SM) and monoglycosylated sphingolipids like galactosylceramides (GalCer) are well documented Our recent investigation showed tubular bilayers in the aqueous dispersions of N-nervonoyl GalCer [N-(24:lΔ15,cls) GalCer] (a major fatty acyl moiety of natural GalCer). To determine the influence of lipid head groups on the resulting mesophasic morphology, we investigated microstructural self-assemblies of N-nervonoyl-SM [N-(24:1 Δ15,cls) SM; the second most abundant sphingomyelin in mammalian cell membranes], 1- palmitoyl-2-nervonoyl phosphatidylcholine [PNPC] (the lipid species with the same acyl chain configuration as in N-(24: 1) GalCer) and also compared it with egg-SM by freeze-fracture EM.Procedures for synthesizing and purifying N-(24:1) GalCer, N-(24:1) SM, and PNPC have been reported . Egg-SM was purchased from Avanti Polar Lipids, Alabaster AL. All lipids were >99% pure as checked by thin layer chromatography. Lipid dispersions were prepared by hydrating dry lipid with phosphate buffer (pH 6.6) at 80-90°C (3-5 min), vigorously vortexing (1 min) and repeating this procedure for three times prior to three freeze-thaw cycles.

scholarly journals Thermodynamics of ion binding and occupancy in potassium channels

2021 ◽  
Author(s):  
Zhifeng Jing ◽  
Joshua A. Rackers ◽  
Lawrence Pratt ◽  
Chengwen Liu ◽  
Susan B. Rempe ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Ion Binding ◽  
Cellular Functions ◽  
Ion Conduction

Potassium channels modulate various cellular functions through efficient and selective conduction of K+ ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of debate....

scholarly journals Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Aimin Yang ◽  
Supansa Pantoom ◽  
Yao-Wen Wu
Keyword(s):  
Legionella Pneumophila ◽  
Lipid Binding ◽  
Effector Protein ◽  
Intracellular Pathogen ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Acyl Chains ◽  
Pathogenic Microbes ◽  
Lir Motif ◽  
Lipid Binding Site

Autophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ α3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus, Legionella has evolved a novel mechanism to specifically evade host autophagy.

scholarly journals Structure, function, and regulation of myosin 1C.

2005 ◽  
Vol 52 (2) ◽  
pp. 373-380 ◽  
Author(s):  
Barbara Barylko ◽  
Gwanghyun Jung ◽  
Joseph P Albanesi
Keyword(s):  
Plasma Membrane ◽  
Binding Sites ◽  
Subcellular Location ◽  
Lipid Binding ◽  
Tail Domain ◽  
Anionic Lipid ◽  
Myosin I ◽  
Docking Proteins ◽  
Neck Domain ◽  
Anionic Lipids

Myosin 1C, the first mammalian single-headed myosin to be purified, cloned, and sequenced, has been implicated in the translocation of plasma membrane channels and transporters. Like other forms of myosin I (of which eight exist in humans) myosin 1C consists of motor, neck, and tail domains. The neck domain binds calmodulins more tightly in the absence than in the presence of Ca(2+). Release of calmodulins exposes binding sites for anionic lipids, particularly phosphoinositides. The tail domain, which has an isoelectic point of 10.5, interacts with anionic lipid headgroups. When both neck and tail lipid binding sites are engaged, the myosin associates essentially irreversibly with membranes. Despite this tight membrane binding, it is widely believed that myosin 1C docking proteins are necessary for targeting the enzyme to specific subcellular location. The search for these putative myosin 1C receptors is an active area of research.

The lipid binding site of the phosphatidylcholine transfer protein from bovine liver

1985 ◽  
Vol 38 (1-2) ◽  
pp. 29-39 ◽  
Author(s):  
D. Van Loon ◽  
Th.A. Berkhout ◽  
R.A. Demel ◽  
K.W.A. Wirtz
Keyword(s):  
Binding Site ◽  
Bovine Liver ◽  
Lipid Binding ◽  
Transfer Protein ◽  
Phosphatidylcholine Transfer Protein ◽  
Lipid Binding Site

The N-Terminus is the Lipid-Binding Site of SAA: Supporting Evidence by MoAbs

1991 ◽  
pp. 83-86
Author(s):  
Yifat Ziq-Bachar ◽  
David Levartowsky ◽  
Mordechaipras ◽  
Alistair F. Strachan ◽  
Mati Fridkin ◽  
...  
Keyword(s):  
Binding Site ◽  
Lipid Binding ◽  
Supporting Evidence ◽  
N Terminus ◽  
Lipid Binding Site
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