MP
Engineered odorant receptors illuminate the basis of odour discrimination.
de March CA, Ma N, Billesbølle CB, Tewari J, Llinas Del Torrent C, van der Velden WJC, Ojiro I, Takayama I, Faust B, Li L, Vaidehi N, Manglik A, Matsunami H.
Nature. 2024 Oct 30. d
oi: 10.1038/s41586-024-08126-0. Epub ahead of print.
PMID: 39478229.
Olfactory system allows vertebrates to detect odors via G protein-coupled odorant receptors (ORs): humans have around 400.
Here: engineered “consensus” ORs representing the major OR subfamilies to model native receptors.
=> structural visualization of odorant binding through cryoEM.
Functionally important binding site for a volatile anesthetic in a voltage-gated sodium channel identified by X-ray crystallography
David Hollingworth, Karl F. Herold, Geoff Kelly, Vitaliy B. Mykhaylyk, Jiaxin Xiang, B. A. Wallace, Hugh C. Hemmings Jr.
bioRxiv 2024.11.04.621342;
doi: https://doi.org/10.1101/2024.11.04.621342
Volatile anesthetics affect MPs and voltage-gated ion channels but mechanisms of action are not fully understood.
Here: bacterial sodium channel NavMs to explore how the anesthetic sevoflurane binds to and influences ion channels => specific binding site within a hydrophobic pocket essential for channel function.
Cryo-EM structure and molecular mechanism of the jasmonic acid transporter ABCG16.
An N, Huang X, Yang Z, Zhang M, Ma M, Yu F, Jing L, Du B, Wang YF, Zhang X, Zhang P.
Nat Plants. 2024 Nov 4.
doi: 10.1038/s41477-024-01839-0. Epub ahead of print.
PMID: 39496849.
Jasmonates = key plant hormones for growth and stress responses.
De Novo Missense Variations of ATP8B2 Impair Its Phosphatidylcholine Flippase Activity.
Takatsu H, Nishimura N, Kosugi Y, Ogawa H, Nakayama K, Colin E, Platzer K, Abou Jamra R, Redler S, Prouteau C, Ziegler A, Shin HW.
Mol Cell Biol. 2024;44(11):473-488.
doi: 10.1080/10985549.2024.2391829. Epub 2024 Sep 2.
PMID: 39219493.
P4-ATPases = lipid flippases that help move lipids across cell membranes, and ATP8B2, a member of this family, specifically flips PC at the plasma membrane.
3 specific genetic variations in ATP8B2 found in patients with intellectual disability reduce its flippase activity without affecting its location or interaction with CDC50A protein partner.
Cryo-EM structure of the Mycobacterium smegmatis MmpL5-AcpM complex.
Maharjan R, Zhang Z, Klenotic PA, Gregor WD, Purdy GE, Yu EW.
mBio. 2024 Oct 31:e0303524.
doi: 10.1128/mbio.03035-24. Epub ahead of print.
PMID: 39480109.
Mycobacterium tuberculosis relies on 13 MmpL transporters, key for its survival, and these proteins are potential drug targets for tuberculosis treatment.
Here: first high-resolution cryo-EM structure of MmpL5, an iron-regulating transporter, bound to AcpM in Mycobacterium smegmatis, showing how these proteins interact in the cytoplasm.
=> MmpL5 may also form a critical complex with MbtL for iron acquisition, essential for the bacterium’s survival and replication.
Substrate recognition and transport mechanism of the PIN-FORMED auxin exporters.
Ung KL, Schulz L, Stokes DL, Hammes UZ, Pedersen BP.
Trends Biochem Sci. 2023 Nov;48(11):937-948.
doi: 10.1016/j.tibs.2023.07.006. Epub 2023 Aug 12.
PMID: 37574372.
Auxins, essential for plant growth, rely on polar auxin transport mediated by PIN-FORMED (PIN) transporters, which export auxin from plant cells.
Here: structures of PIN1, PIN3, and PIN8 transporters, showing how they recognize and transport auxin through inward- and outward-facing conformations.
Comparative analysis suggests “elevator” transport mechanism.
GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states.
Liu F, Zhou H, Li X, Zhou L, Yu C, Zhang H, Bu D, Liang X.
BMC Bioinformatics. 2024 Nov 4;25(1):343.
doi: 10.1186/s12859-024-05962-9.
PMID: 39497074.
GPCR-BSD = database containing 127,990 predicted binding sites across 803 GPCRs in both active and inactive states, identified using fpocket, CavityPlus, and GHECOM methods.
The database, accessible online, enables users to query, visualize, and compare binding sites.
Membranes
Protocells by spontaneous reaction of cysteine with short-chain thioesters.
Cho CJ, An T, Lai YC, Vázquez-Salazar A, Fracassi A, Brea RJ, Chen IA, Devaraj NK.
Nat Chem. 2024 Oct 30.
doi: 10.1038/s41557-024-01666-y. Epub ahead of print.
PMID: 39478161.
A reaction between the amino acid cysteine with short-chain carbon molecules forms small, two-tailed lipids that spontaneously arrange themselves into a membrane-like sphere.
Mitochondrial membrane lipids in the regulation of bioenergetic flux.
Decker ST, Funai K.
Cell Metab. 2024 Sep 3;36(9):1963-1978.
doi: 10.1016/j.cmet.2024.07.024. Epub 2024 Aug 22.
PMID: 39178855.
Oxidative phosphorylation relies on the unique lipid composition of the IMM, which is maintained by localized biosynthetic enzymes and specific lipid transporters.
Here: review exploring mitochondrial lipids’ roles in bioenergetics, their biosynthetic pathways, implications in human disease, and regulatory mechanisms affecting mitochondrial energy production.
Free Fatty Acids Inhibit An Ion-Coupled Membrane Transporter By Dissipating The Ion Gradient.
Wang X, Rusinova R, Gregorio GG, Boudker O.
J Biol Chem. 2024 Nov 2:107955. doi: 10.1016/j.jbc.2024.107955. Epub ahead of print. PMID: 39491650.
Glutamate transporters regulate synaptic glutamate levels for proper brain function, and certain unsaturated FA, like arachidonic acid (AA) and docosahexaenoic acid (DHA), modulate these transporters.
Here: study shows that AA and DHA inhibit glutamate uptake by causing cation leaks => disruption of the sodium gradient required for transporter function, without affecting the transporters’ structural transitions.
=> FA can act as cation ionophores, broadly modulating membrane channels and ion-coupled transporters.
Revised diffusion law permits quantitative nanoscale characterization of membrane organization
Barbora Svobodova, David Stastny, Hans Blom, Dr. Ilya I. Mikhalyov, Dr. Natalia Gretskaya, Dr. Alena Ballekova, Dr. Erdinc Sezgin, Prof. Martin Hof, Dr. Radek Sachl
bioRxiv 2024.11.01.621464;
doi: https://doi.org/10.1101/2024.11.01.621464
Previous techniques like STED-FCS could only identify the presence of plasma membranes and not crucial parameters like size, surface fraction, or lipid diffusion rates.
Here: new method based on a revised diffusion law to extract five key parameters from STED-FCS data, including in- and outside-domain diffusion and self-diffusion rates.
Metal ion cofactors modulate integral enzyme activity by varying differential membrane curvature stress.
Piller P, Reiterer P, Semeraro EF, Pabst G.
RSC Appl Interfaces. 2024 Oct 25.
doi: 10.1039/d4lf00309h. Epub ahead of print.
PMID: 39479198.
Metal ions, such as calcium, are known to stabilize the active form of membrane enzymes like OmpLA.
Here: in charge-neutral membranes, OmpLA is more active in symmetric bilayers due to reduced curvature stress, but this effect is reversed in charged membranes, where calcium ions alter lipid shape (reduction of the curvature stress, enhancing of the enzyme activity).
=> ion cofactors modulate membrane protein activity not only through direct interactions but also by influencing the molecular shape of charged lipids !
All-atom simulations elucidate the molecular mechanism underlying RNA-membrane interactions
Salvatore Di Marco, Jana Aupič, Giovanni Bussi, Alessandra Magistrato
bioRxiv 2024.11.01.618995;
doi: https://doi.org/10.1101/2024.11.01.618995
RNA molecules were recently discovered to be present on the extracellular surface of living cells, where they mediate intercellular signalling + RNA-membrane interactions influence the efficacy of lipid-based RNA delivery systems.
Here: study showing how RNA-phospholipid membrane interactions occur, by means of all-atom simulations.
Guanine = strongest interaction with the membrane due to extensive hydrogen bond formation.
intra-RNA base pairing present in organised RNA structures significantly hinders RNA binding to the membrane.
Molecular probes for tracking lipid droplet membrane dynamics.
Kong L, Bai Q, Li C, Wang Q, Wang Y, Shao X, Wei Y, Sun J, Yu Z, Yin J, Shi B, Fang H, Chen X, Chen Q.
Nat Commun. 2024 Oct 31;15(1):9413.
doi: 10.1038/s41467-024-53667-7.
PMID: 39482302.
Lipid droplets = unique monolayer lipid membrane, but studying it has been challenging due to a lack of suitable molecular probes.
Here: LDM = novel probe that targets LD membranes by activating in the specific HClO/ClO- microenvironment around LDs, allowing for visualization of the ring-like LD membrane and protein accumulation.
Enables imaging of LD membranes in live cells.
Evaluating the Impact of the Membrane Thickness on the Function of the Intramembrane Protease GlpG.
Engberg O, Mathath AV, Döbel V, Frie C, Lemberg MK, Chakraborty D, Huster D.
Biophys J. 2024 Nov 1:S0006-3495(24)00707-0.
doi: 10.1016/j.bpj.2024.10.019. Epub ahead of print.
PMID: 39488732.
E. coli rhomboid intramembrane protease GlpG used to explore how membrane thickness affects protein activity.
GlpG activity is influenced by cholesterol content and membrane composition
Methods
In-Cell DEER Spectroscopy of Nanodisc-Delivered Membrane Proteins in Living Cell Membranes.
Cheng CC, Tsai RF, Lin CK, Tan KT, Kalendra V, Simenas M, Lin CW, Chiang YW.
JACS Au. 2024 Sep 24;4(10):3766-3770.
doi: 10.1021/jacsau.4c00702.
PMID: 39483229.
Nnanodelivery method using NDs to transport spin-labeled membrane proteins into living cells, enabling DEER spectroscopy.
Method applied to BsYetJ, revealing its conformational changes and calcium ion transport activity in both E. coli and B. subtilis membranes.
=> impact of lipid composition on protein structure, offering a new approach to study membrane proteins in more physiologically relevant environments.
An ATP detection system based on the enzyme reaction with biotin protein ligase.
Sueda S, Fujii S.
Anal Biochem. 2024 Oct 24;696:115698.
doi: 10.1016/j.ab.2024.115698. Epub ahead of print.
PMID: 39461694.
Novel ATP detection system combining biotinylation from Sulfolobus tokodaii with FRET. The system uses the biotin protein ligase and biotin carboxyl carrier protein fused to fluorescent proteins, where ATP is detected by monitoring the FRET signal between them.
=> successfully detection of ATP as low as 5 nM, with the advantage of signal stability for at least 2 hours, unlike traditional luciferase-based ATP assays.
Memprot.GPCR-ModSim: Modelling and simulation of membrane proteins in a nutshell.
van den Broek RL, Bello X, Küpper RV, van Westen GJP, Jespers W, Gutiérrez-de-Terán H.
Bioinformatics. 2024 Nov 6:btae662.
doi: 10.1093/bioinformatics/btae662. Epub ahead of print.
PMID: 39504465.
Memprot.GPCR-ModSim = web server supporting the modeling and simulation of any membrane protein system.
It accepts either a MP sequence to generate an AlphaFold model or a 3D structure. The server’s molecular dynamics protocol prepares the system by embedding it in a membrane, solvatating, and equilibrating it for use in further simulations, such as ligand-binding free energy calculations.
Miscellaneous
‘We need to be ready for a new world’: scientists globally react to Trump election win.
Tollefson J.
Nature. 2024 Nov 6.
doi: 10.1038/d41586-024-03635-4. Epub ahead of print.
PMID: 39506173.
‘A big, big win’: plan to pay for wildlife conservation emerges at biodiversity summit.
Taylor L.
Nature. 2024 Nov 4.
doi: 10.1038/d41586-024-03609-6. Epub ahead of print.
PMID: 39496860.
Amid fights over conservation funding, an agreement is reached for businesses to pay for profiting from digital genetic information taken from nature.
A numerical evaluation of the Finite Monkeys Theorem
Stephen Woodcock, Jay Falletta.
Franklin Open Volume 9, December 2024, 100171
You may have heard the adage that a monkey pressing the keys of a typewriter at random is bound to end up writing the complete works of William Shakespeare … Is it true ? have a look to this paper to know more.
Long story short: yes but no.
interesting thread on Twitter here by @astropierre:
https://twitter.com/astropierre/status/1853398184183103805
A molecular mechanism for bright color variation in parrots.
Arbore R, Barbosa S, Brejcha J, Ogawa Y, Liu Y, Nicolaï MPJ, Pereira P, Sabatino SJ, Cloutier A, Poon ESK, Marques CI, Andrade P, Debruyn G, Afonso S, Afonso R, Roy SG, Abdu U, Lopes RJ, Mojzeš P, Maršík P, Sin SYW, White MA, Araújo PM, Corbo JC, Carneiro M.
Science. 2024 Nov;386(6721):eadp7710.
doi: 10.1126/science.adp7710. Epub 2024 Nov 1.
PMID: 39480920.
The bright coloration of parrots is known to be determined by pigments known as psittacofulvins.
Here: gene expression, chromatin accessibility, and genome-wide association studies to identify the genetic underpinning of red and yellow coloration in the dusky lory.
A solution to the anti-Bredt olefin synthesis problem.
McDermott L, Walters ZG, French SA, Clark AM, Ding J, Kelleghan AV, Houk KN, Garg NK.
Science. 2024 Nov;386(6721):eadq3519.
doi: 10.1126/science.adq3519. Epub 2024 Nov 1.
PMID: 39480919.
Chemists have synthesized a class of molecules previously thought too unstable to exist. The molecules, called anti-Bredt olefins (ABOs) contain a double bond between carbon atoms where two carbon rings join together, called the bridgehead position. The 100-year old Bredt’s rule states that this double bond was impossible, as it contorts the molecule into a strained 3D shape that makes it highly reactive and unstable.
Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity.
Sakamoto K, Butera MA, Zhou C, Maurizi G, Chen B, Ling L, Shawkat A, Patlolla L, Thakker K, Calle V, Morgan DA, Rahmouni K, Schwartz GJ, Tahiri A, Buettner C.
Cell Metab. 2024 Oct 15:S1550-4131(24)00376-0.
doi: 10.1016/j.cmet.2024.09.012. Epub ahead of print.
PMID: 39437790.
Faulty insulin activity might not be driving diabetes in people with obesity, a new study hints. Instead, consuming a high-fat diet triggers a surge of neurotransmitters across the body, leading to the rapid breakdown of fatty tissue in the liver. The liberation of high levels of fatty acids is linked to a host of health conditions, from diabetes to liver failure. Mice engineered to produce less neurotransmitters and fed a high-fat diet gained as much weight as unmodified mice, and maintained similar insulin signalling activity, but did not develop insulin resistance. “This is indeed a paradigm shift,” says biochemist Martina Schweiger.
A robot retrieves the first melted fuel from Fukushima nuclear reactor
A remote-controlled robot has successfully collected a tiny piece of melted nuclear fuel from the inside of the Fukushima Daiichi nuclear power plant, which was shut down after suffering major damage in an earthquake and tsunami in 2011. The robot clipped a piece of fuel that weighed less than 3 grams from inside the Unit 2 reactor core and brought it back to assess its radioactivity. Analysing the melted fuel debris is essential to determine how best to remove, store and dispose of the roughly 800 tonnes that remain.
World’s first wooden satellite, developed in Japan, heads to space
Kantaro Komiya and Irene Wang