Membrane’s digest
MP
Bidirectional ATP-driven transport of cobalamin by the mycobacterial ABC transporter BacA.
Nijland M, Lefebvre SN, Thangaratnarajah C, Slotboom DJ.
Nat Commun. 2024 Mar 23;15(1):2626.
doi: 10.1038/s41467-024-46917-1. PMID: 38521790.
BacA, a mycobacterial ABC transporter, transports cobalamin and various hydrophilic compounds across the lipid bilayer bidirectionally, challenging the conventional understanding of ABC transporter functionality. Through fluorescence-based transport assays, it was discovered that BacA facilitates both import and export of cobalamin, suggesting a unique mechanistic role (BacA transports cobalamin in both the import and export direction) and potential evolutionary advantages for microbial communities.
Structure and function of the Arabidopsis ABC transporter ABCB19 in brassinosteroid export.
Ying W, Wang Y, Wei H, Luo Y, Ma Q, Zhu H, Janssens H, Vukašinović N, Kvasnica M, Winne JM, Gao Y, Tan S, Friml J, Liu X, Russinova E, Sun L.
Science. 2024 Mar 22;383(6689):eadj4591.
doi: 10.1126/science.adj4591. Epub 2024 Mar 22. PMID: 38513023.
Brassinosteroids (= essential phytohormones regulating plant development and stress response) exported from the cell interior to the cell surface by ABC transporter ABCB19.
Structural analysis and transport assays => ABCB19 mediates the export of bioactive brassinosteroids. Crucial mechanism tightly linked to brassinosteroid signaling in plants, with implications for understanding plant adaptation to environmental cues.
Structural insights into human EMC and its interaction with VDAC.
Li M, Zhang C, Xu Y, Li S, Huang C, Wu J, Lei M.
Aging (Albany NY). 2024 Mar 15;16.
doi: 10.18632/aging.205660. Epub ahead of print. PMID: 38517390.
The ER membrane protein complex (EMC) = conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking MPs.
Here: cryoEM structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states.
=> specific interaction between VDAC and EMC at mitochondria-ER contact sites (conserved from yeast to humans) + gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion.
EMC = insertase in the VDAC1-bound state ?
Structural and mechanistic basis of the central energy-converting methyltransferase complex of methanogenesis.
Aziz I, Kayastha K, Kaltwasser S, Vonck J, Welsch S, Murphy BJ, Kahnt J, Wu D, Wagner T, Shima S, Ermler U.
Proc Natl Acad Sci U S A. 2024 Apr 2;121(14):e2315568121.
doi: 10.1073/pnas.2315568121. Epub 2024 Mar 26. PMID: 38530900.
Methanogenic archaea, crucial for global biogeochemical cycles.
Methane-producing energy metabolism is catalyzed by M methyltransferase (MtrABCDEFGH), coupling Na+ transport with methyl transfer via a cobamide prosthetic group.
Here: 2.08 Å cryo-EM structure of Mtr(ABCDEFG)3 => complex arrangement with central Mtr(ABFG)3 stalk flanked by membrane-spanning MtrCDE globes, suggesting a mechanism fordemethylation and coenzyme M methylation half-reactions.
Modeling => mechanism where methyl-cob(III)amide drives inward-facing conformation, Na+ flux, and coenzyme M methylation, while regeneration occurs through large-scale shuttling movements of the vitamin B12-carrying domain.
Membranes
Limitations in membrane protein structure determination by lipid nanodiscs.
Zhao C.
Trends Biochem Sci. 2024 Mar 26:S0968-0004(24)00076-8.
doi: 10.1016/j.tibs.2024.03.010. Epub ahead of print. PMID: 38538407.
NDs = popular mimetics of biological membranes for determining MP structures. However, a recent study revealed that the choice of ND scaffold directly influences the structure of an ion channel. This finding prompts us to be cautious and calls for improved membrane mimetics for structure determination.
Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia.
Chaptal MC, Maraninchi M, Musto G, Mancini J, Chtioui H, Dupont-Roussel J, Marlinge M, Fromonot J, Lalevee N, Mourre F, Beliard S, Guieu R, Valero R, Mottola G.
Cells. 2024 Mar 11;13(6):488.
doi: 10.3390/cells13060488. PMID: 38534331.
Elevated levels of LDL-cholesterol (LDL-C) => link to atherosclerosis, primarily through promoting foam cell buildup in vessels.
Here: investigation of the expression of adenosine A2A receptor (A2AR) and Flotillin-1, both cholesterol-sensitive proteins, in untreated hypercholesterolemia (HC) patients and healthy participants.
=> lower A2AR and Flotillin-1 HC patients, negatively correlated with LDL-C levels, suggesting LDL-C’s impact on cholesterol-enriched membrane microdomains and potentially broader cardiovascular toxicity.
Exploring membrane asymmetry and its effects on membrane proteins.
Pabst G, Keller S.
Trends Biochem Sci. 2024 Feb 13:S0968-0004(24)00021-5.
doi: 10.1016/j.tibs.2024.01.007. Epub ahead of print. PMID: 38355393.
Review on recent advancements in understanding plasma membrane asymmetry, facilitated by compositionally controlled asymmetric model membranes.
Experimental and computational studies have elucidated the mechanisms governing structural and dynamic coupling between distinct bilayer leaflets, influencing membrane bending rigidity and lipid domain formation.
Moreover, evidence suggests that integral membrane proteins exhibit asymmetric properties in response to lipid distributions.
The Chemical Reactivity of Membrane Lipids.
Duché G, Sanderson JM.
Chem Rev. 2024 Mar 27;124(6):3284-3330.
doi: 10.1021/acs.chemrev.3c00608. Epub 2024 Mar 18.
PMID: 38498932.
Review describing the chemical reactivity exhibited by lipids in their membrane form, with an emphasis on conditions where the lipids are well hydrated in the form of bilayers.
Key topics: lytic reactions of glyceryl esters, aminolysis, and transesterification; oxidation reactions of alkenes in unsaturated fatty acids and sterols; reactivity of headgroups, particularly with reactive carbonyl species; and E/Z isomerization of alkenes.
The consequences of reactivity for biological activity and biophysical properties are also discussed.
Molecules
Solubilization of Phospholipid by Surfactin Leading to Lipid Nanodisc and Fibrous Architecture Formation.
Imura T, Yanagisawa S, Ikeda Y, Moriyama R, Sakai K, Sakai H, Taira T.
Molecules. 2024 Mar 14;29(6):1300.
doi: 10.3390/molecules29061300. PMID: 38542936.
Study of the self-assembly of a mixture of bio-derived cyclic peptide, surfactin (SF), and DMPC.
=> SF induces the solubilization of DMPC MLVs to form their nanodiscs, which was confirmed by SEC, DLS, and TEL.
7.10 MAG. A Novel Host Monoacylglyceride for In Meso (Lipid Cubic Phase) Crystallization of Membrane Proteins
Pawel Krawinski, Luke Smithers, Leendert van Dalsen, Coilin Boland, Nikita Ostrovitsa, Javier Pérez, and Martin Caffrey*
Cryst. Growth Des. 2024, Publication Date:March 25, 2024
A novel monoacylglycerol, 7.10 MAG, has been produced for use in LCP crystallization of MPs.
7.10 MAG differs from monoolein: shorter in chain length by one methylene and its cis olefinic bond is two carbons closer to the glycerol headgroup => alter the phase behavior of the hydrated lipid and the microstructure of the corresponding mesophases formed. Phase diagrams have been constructed (they include lamellar crystalline, fluid isotropic, lamellar liquid-crystalline, cubic-Ia3d, and cubic-Pn3m phases, as observed with monoolein).
Absence in the inverted hexagonal phase is rationalized on the basis of 7.10 MAG’s chemical constitution.
Monitoring the conformational ensemble and lipid environment of a mechanosensitive channel under cyclodextrin-induced membrane tension.
Lane BJ, Ma Y, Yan N, Wang B, Ackermann K, Karamanos TK, Bode BE, Pliotas C.
Structure. 2024 Mar 21:S0969-2126(24)00080-7.
doi: 10.1016/j.str.2024.02.020. Epub ahead of print. PMID: 38521071.
Membrane forces = crucial role in shifting the equilibria of mechanosensitive channels (translation of mechanical stimuli into electrical signals).
Here: us of cyclodextrins to mimic tension in membranes and investigate the conformational dynamics, lipid environment, and functional aspects of MscS through EPR spectroscopy, NMR, and electrophysiology techniques.
Polymer-extracted structure of the mechanosensitive channel MscS reveals the role of protein-lipid interactions in the gating cycle
Elissa Moller, Madolyn Britt, Fei Zhou, Hyojik Yang, Andriy Anshkin, Robert Ernst, Sergei Sukharev, Doreen Matthies
bioRxiv 2024.01.22.576751;
doi: https://doi.org/10.1101/2024.01.22.576751
3 Å MscS structure of E. coli MscS obtained with Glyco-DIBMA polymer extraction, eliminating the lipid removal step that is common to all previous structures.
=> protein in non-conductive conformation + well-resolved densities of four endogenous phospholipid molecules intercalating between the lipid-facing and pore-lining helices in preferred orientations. Mutations altering lipid coordination inhibit MscS inactivation, while charge removal near the lipid-filled crevice enhances inactivation, suggesting a novel inactivation mechanism involving uncoupling of tension-sensing helices from the gate.
Miscellaneous
Predicting and improving complex beer flavor through machine learning.
Schreurs M, Piampongsant S, Roncoroni M, Cool L, Herrera-Malaver B, Vanderaa C, Theßeling FA, Kreft Ł, Botzki A, Malcorps P, Daenen L, Wenseleers T, Verstrepen KJ.
Nat Commun. 2024 Mar 26;15(1):2368.
doi: 10.1038/s41467-024-46346-0. PMID: 38531860.
Chemical and sensory analyses of 250 different beers to train machine learning models that allow predicting flavor and consumer appreciation.
For each beer, measurement of over 200 chemical properties, quantitative descriptive sensory analysis with a trained tasting panel and map data from over 180,000 consumer reviews to train 10 different machine learning models.
‘After you’: first symbolic gesture in birds
Scientific American
Reference: Current Biology paper
Suzuki TN et al. Curr Biol. 2024
doi: 10.1016/j.cub.2024.01.030. PMID: 38531311.
Japanese tits (Parus minor) flutter their wings to invite their mate to enter the nest first. Scientists who observed eight breeding pairs of wild tits noticed that when one of the birds sat in front of the next box and fluttered its wings, the other would go in first.
Rethinking Cryo-Electron Microscopy: From Structural Biology to Climate Solutions in the AI Era
Fowls, A. T., & Kidding, J. E. (2024).
Journal of Structural Biology Advances, 12(3), 321-336.
Recent advances in artificial intelligence (AI) have precipitated a paradigm shift in the field of structural biology, heralding a new era of computational prowess that challenges the traditional dominance of cryo-electron microscopy (cryo-EM). The convergence of AI-driven methodologies with structural determination techniques has sparked a revolution in biomolecular research, unleashing unprecedented capabilities for deciphering the intricate architecture of macromolecular complexes.
In this study, authors elucidate the transformative impact of AI on structural biology and its implications for the future of cryo-EM.
The emergence of AI-driven structural prediction tools has catalyzed a shift towards in silico methods, offering rapid and cost-effective alternatives to traditional structural determination techniques, circumventing the need for labor-intensive experimental procedures and relegating cryo-EM to a supplementary role in structural biology research.
As the scientific community embraces the capabilities of AI in structural determination, the utility of cryo-EM microscopes is being reevaluated, prompting discussions on their future utilization. In light of this paradigm shift, we propose a novel avenue for repurposing now outdated cryo-EM instruments. Leveraging the principles of thermodynamics and refrigeration, we propose a novel application for decommissioned cryo-EM instruments. Through theoretical modeling and feasibility studies, we demonstrate the potential of cryo-EM microscopes to serve as efficient refrigeration units to combat rising global temperatures, leveraging their inherent cryogenic capabilities to regulate environmental temperatures. By repurposing these once cutting-edge instruments, April T. Fowls and Jest E. Kidding envision a sustainable solution for reducing greenhouse gas emissions and mitigating the adverse effects of climate change.
PhosAF: An integrated deep learning architecture for predicting protein phosphorylation sites with AlphaFold2 predicted structures.
Yu Z, Yu J, Wang H, Zhang S, Zhao L, Shi S.
Anal Biochem. 2024 Mar 19;690:115510.
doi: 10.1016/j.ab.2024.115510. PMID: 38513769.
Building upon AlphaFold2, a novel integrated deep learning architecture PhosAF is developed to predict phosphorylation sites in human proteins
Experimental results on independent test data and case study indicate that model PhosAF surpasses the current most advanced methods in phosphorylation site prediction.
Tweeting your research paper boosts engagement but not citations.
Nogrady B.
Nature. 2024 Mar 27.
doi: 10.1038/d41586-024-00922-y. Epub ahead of print.
PMID: 38532166.
Analysis of a random selection of papers shared on social media showed no causative link between posting and citations.
These levitating bubbles are long-lived and puncture-proof.
Nature. 2024 Apr;628(8006):11.
doi: 10.1038/d41586-024-00859-2. PMID: 38532164.