MP
The stromal side of the cytochrome b6f complex regulates state transitions.
Riché A, Dumas L, Malesinski S, Bossan G, Madigou C, Zito F, Alric J.
Plant Cell. 2024 Jul 4:koae190.
doi: 10.1093/plcell/koae190. Epub ahead of print.
PMID: 38963887.
In oxygenic photosynthesis => regulation of the state transitions involves reduction of the plastoquinone (PQ) pool, activation of STT7 by b6f, and phosphorylation and migration of LHCII.
Here: authors show that in Chlamydomonas reinhardtii, the C-terminus of the cyt b6 subunit PetB acts on phosphorylation of STT7 and state transitions. (site-directed mutagenesis of petB => salt bridge between cyt b6 (PetB) and subunit IV (PetD) is key to the assembly of the complex + highly phosphorylated forms of STT7 accumulate transiently after reduction of the PQ pool => they represent the active forms of the protein kinase.
Phosphorylation of the LHCII targets is favored at the expense of the protein kinase, and the migration of LHCII towards PSI is the limiting step for state transitions.
Proton-coupled transport mechanism of the efflux pump NorA.
Li J, Li Y, Koide A, Kuang H, Torres VJ, Koide S, Wang DN, Traaseth NJ.
Nat Commun. 2024 May 27;15(1):4494.
doi: 10.1038/s41467-024-48759-3.
PMID: 38802368.
Proton-coupling mechanism of the NorA efflux pump from SA by cryoEM structures in various protonation states of two essential acidic residues.
The two acidic residues serve as a “belt and suspenders” protection mechanism to prevent simultaneous binding of protons and drug => enforced coupling stoichiometry and antibiotic resistance.
Effects of pH on opioid receptor activation and implications for drug design.
Stein C, Berlin CU, Franklin CB.
Biophys J. 2024 Jul 5:S0006-3495(24)00446-6.
doi: 10.1016/j.bpj.2024.07.007. Epub ahead of print.
PMID: 38970252.
Studies on opioids indicate that ligand – receptor interactions are very different in diseased tissues compared to normal situations. In such microenvironments, protons play an important role in structural and functional alterations of both ligands and receptors. => future drug design should take these aspects into account in order to reduce adverse side effects while preserving desired effects of novel compounds.
Structures and Efflux Mechanisms of the AcrAB-TolC Pump.
Yu Z, Shi X, Wang Z.
Subcell Biochem. 2024;104:1-16.
doi: 10.1007/978-3-031-58843-3_1.
PMID: 38963480.
Previous studies on AcrAB TolC’s structure have been limited to individual components or in vitro determination of fully assembled pumps. Recent advancements in cellular cryo-ET => novel insights into this pump’s assembly and functional mechanism within its native cell membrane environment.
Here: summary of the structural data regarding the AcrAB-TolC efflux pump.
Functionality of chimeric TssA proteins in the type VI secretion system reveals sheath docking specificity within their N-terminal domains.
Fecht S, Paracuellos P, Subramoni S, Tan CAZ, Ilangovan A, Costa TRD, Filloux A.
Nat Commun. 2024 May 20;15(1):4283.
doi: 10.1038/s41467-024-48487-8.
PMID: 38769318.
PA = 3 type VI secretion systems, each comprising a dozen distinct proteins.
TssA = least conserved T6SS component, has variations in size which influence domain organisation and structure.
Here: TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation.
=> proposition of a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position.
Membrane
Quantification of membrane geometry and protein sorting on cell membrane protrusions using fluorescence microscopy.
Yang S, Shi Z.
Methods Enzymol. 2024;700:385-411.
doi: 10.1016/bs.mie.2024.01.023. Epub 2024 Apr 16.
PMID: 38971608.
Plasma membranes are flexible and can exhibit numerous shapes below the optical diffraction limit.
Here: use of simple widefield fluorescence microscopy to study the geometrical properties (i.e., radius, length, and number) of thin membrane protrusions.
Applications of phase-separating multi-bilayers in protein-membrane domain interactions.
Wang HY, Dey S, Levental KR.
Methods Enzymol. 2024;700:275-294.
doi: 10.1016/bs.mie.2024.04.024.
PMID: 38971603.
Description of model membrane with multiple lipid bilayers stacked on a mica substrate that is prepared through a spin-coating technique.
=> useful in the study of phase separated membranes with a high cholesterol content, mobile lipids, microscopic and reversible phase separation, and easy conjugation with proteins.
Molecules
Characterization of size-tuneable aescin-lipid nanoparticles as platform for stabilization of membrane proteins.
Escobedo F, Gospalswamy M, Hägerbäumer P, Stank TJ, Victor J, Groth G, Gohlke H, Dargel C, Hellweg T, Etzkorn M.
Colloids Surf B Biointerfaces. 2024 Jul 3;242:114071.
doi: 10.1016/j.colsurfb.2024.114071. Epub ahead of print.
PMID: 39002202.
Disc-like lipid nanoparticles stabilized by saponin biosurfactants display interesting properties, including their temperature-driven re-organization.
β-Aescin = saponin from seed extract of the horse chestnut tree.
β-Aescin allows for strong interactions with lipid membranes + beneficial therapeutic implications + ability to decompose continuous lipid membranes into size-tuneable discoidal NPs.
Here: characterization of lipid NPs formed by aescin and DMPC (modulations by temperature and aescin content + MP solub PoC with BR).
Ligand-Directed Labeling of the Adenosine A1 Receptor in Living Cells.
Comeo E, Goulding J, Lin CY, Groenen M, Woolard J, Kindon ND, Harwood CR, Platt S, Briddon SJ, Kilpatrick LE, Scammells PJ, Hill SJ, Kellam B.
J Med Chem. 2024 Jul 12.
doi: 10.1021/acs.jmedchem.4c00835. Epub ahead of print.
PMID: 38994645.
Rational design, development, and application of the first ligand-directed chemistry approach for labeling the A1AR in living cells: covalent labeling of A1AR expressed in living cells while the orthosteric binding site remains available (confocal microscopy and FCS to study A1AR localization and dynamics in living cells).
Methods
Free-Standing DNA Origami Superlattice to Facilitate Cryo-EM Visualization of Membrane Vesicles.
Aissaoui N, Mills A, Lai-Kee-Him J, Triomphe N, Cece Q, Doucet C, Bonhoure A, Vidal M, Ke Y, Bellot G.
J Am Chem Soc. 2024 May 15;146(19):12925-12932.
doi: 10.1021/jacs.3c07328. Epub 2024 May 1.
PMID: 38691507.
Difficulties in preparing holey carbon cryo-EM grids with low vesicle heterogeneities, at low concentration and with kinetic control of the chemical reactions or assembly processes, have limited cryo-EM use in the extracellular vesicles study.
Here: membrane vesicle cryo-EM sample preparation method using a free-standing DNA-affinity superlattice for covering holey carbon cryo-EM grids (cholesterol-binding sites to specifically trap membrane vesicles).
Asymmetric Lipid Bilayers and Potassium Channels Embedded Therein in the Contact Bubble Bilayer.
Matsuki, Y., Iwamoto, M., Oiki, S. (2024).
Methods in Molecular Biology, vol 2796. Humana, New York, NY.
https://doi.org/10.1007/978-1-0716-3818-7_1Microbio
Complexity of native cell membranes => bottom-up approach from simplified synthetic membranes are necessary.
Recent technological advancements => development of asymmetric membranes: the contact bubble bilayer (CBB) method allows single-channel current recordings under arbitrary lipid compositions in asymmetric bilayers.
Here: experimental protocol for the formation of asymmetric membranes using the CBB method with KcsA potassium channel as prototypical model channel.
Authors present a novel lipid perfusion technique that allows rapidly changing the lipid composition while monitoring the single-channel behavior.
In addition: a leaflet perfusion method for modifying the composition of individual leaflets is presented.
Elucidating the complex membrane binding of a protein with multiple anchoring domains using extHMMM.
Madsen JJ, Ohkubo YZ.
PLoS Comput Biol. 2024 Jul 8;20(7):e1011421.
doi: 10.1371/journal.pcbi.1011421. Epub ahead of print.
PMID: 38976709.
Understanding the specific interactions between proteins and membranes = challenging endeavor.
Here: using the membrane binding of Coagulation factor Va (FVa) is investigated.
An updated version of the HMMM model, termed extHMMM, is employed for efficiently observing membrane bindings of systems containing the whole FVa molecule.
Machine Learning Derived Collective Variables for the Study of Protein Homodimerization in Membrane.
Majumder A, Straub JE.
J Chem Theory Comput. 2024 Jul 9;20(13):5774-5783.
doi: 10.1021/acs.jctc.4c00454. Epub 2024 Jun 25.
PMID: 38918177.
The accurate calculation of equilibrium constants for protein-protein association is of fundamental importance to quantitative biology and remains an outstanding challenge for computational biophysics. Traditionally computed from 1D free energy surfaces derived from sampling along a single collective variable.
Here: application of 2 ML methods for the unbiased determination of collective variables for enhanced sampling and analysis of protein-protein association => validation of prior work + demonstration of the effectiveness of the ML methods for the identification of collective variables for association reactions in complex biomolecular systems.
Advanced applications of Nanodiscs-based platforms for antibodies discovery.
Baskakova KO, Kuzmichev PK, Karbyshev MS.
Biophys Chem. 2024 Jul 10;313:107290.
doi: 10.1016/j.bpc.2024.107290. Epub ahead of print.
PMID: 39002246.
Ab are ideal candidates for targeting complex MPs but generating specific and effective Abs targeting these proteins is no easy task.
Lipid nanoparticle systems for retrieving the membrane antigen has been implemented to simplify the therapeutic antibody discovery approach.
This review underscores the advantages of targeting complex MPs with Abs and designing MP antigens.
Microbio
Antibiotic resistance alters the ability of Pseudomonas aeruginosa to invade bacteria from the respiratory microbiome.
Selina Lindon, Sarah Shah, Danna R Gifford, Cédric Lood, Maria A Gomis Font, Divjot Kaur, Antonio Oliver, R Craig MacLean, Rachel M Wheatley,
Evolution Letters, 2024;, qrae030,
https://doi.org/10.1093/evlett/qrae030
Study how antibiotic resistance impacts the ability of a bacterial pathogen to interact with and invade communities of other bacteria present in the body.
=> experiment to link specific antibiotic resistance mutations to changes in the ability of a bacterial pathogen to invade populations of different bacteria from the respiratory microbiome.
Certain antibiotic resistance mutations => increase or decrease the ability of a bacterial pathogen to invade bacteria from the respiratory microbiome.
The impact of antibiotic resistance mutations in bacterial pathogens is not uniform and can vary depending on the other bacteria present in the infected tissue.
Machine Learning Prediction of Small Molecule Accumulation in Escherichia Coli Enhanced with Descriptor Statistics.
Milenkovic S, Boi S, Scorciapino MA, Bodrenko IV, Ceccarelli M.
J Chem Theory Comput. 2024 Jul 8.
doi: 10.1021/acs.jctc.4c00406. Epub ahead of print.
PMID: 38978185.
Prediction of small molecule accumulation in Gram-negative bacteria by using ML techniques enhanced with statistical descriptors derived from MD.
Inclusion of statistical descriptors significantly improves model performance across various prediction metrics.
=> insights into the complex dynamics of antibiotic accumulation in E. coli (generalizable to other Gram-negative species).
Fuzheng Touxie Jiedu Huayu Decoction inhibits the MexAB-OprM efflux pump and quorum sensing-mediated biofilm formation in difficult-to-treat multidrug resistance Pseudomonas aeruginosa.
Liu T, Xu H, Huang T, Liu G, Cao H, Lin Y, Li Y, Li Y, Yao X.
J Ethnopharmacol. 2024 Oct 5;332:118365.
doi: 10.1016/j.jep.2024.118365. Epub 2024 May 23.
PMID: 38796070.
Fuzheng Touxie Jiedu Huayu Decoction (FTJHD) = commonly used clinical formula that has been found effective in resisting multidrug resistance-PA in previous in vivo and in vitro studies.
Here: antimicrobial effects of FTJHD and its drug-containing serum alone or in combination with ceftazidime on difficult-to-treat MDR-PA (DTMDR-P. aeruginosa): tube dilution method and bacterial growth curves, transmission electron microscopy, biofilm formation ability + expression of the mexAB-oprM and QS genes (QPCR) + molecular docking.
=> FTJHD can exert synergistic anti-DTMDR-PA effects with ceftazidime by inhibiting biofilm formation mediated by the MexAB-OprM efflux pump and quorum sensing.
Miscellaneous
Scientists relieved by far-right defeat in French election – but they still face uncertainty.
Casassus B.
Nature. 2024 Jul 8.
doi: 10.1038/d41586-024-02260-5. Epub ahead of print.
PMID: 38982252.
Scientists in France who spoke to Nature have expressed relief that the right-wing party National Rally was defeated in parliamentary elections. But the absence of a clear winner presents uncertainty for scientists, and many do not believe that the new government will make a positive difference to research and higher education. “Science and education were absent from the European and French parliamentary election campaigns, and budget constraints mean that research will not be a priority,” says paediatric immunologist and French Academy of Sciences president Alain Fischer.
Chemical recycling of mixed textile waste.
Andini E, Bhalode P, Gantert E, Sadula S, Vlachos DG.
Sci Adv. 2024 Jul 5;10(27):eado6827.
doi: 10.1126/sciadv.ado6827. Epub 2024 Jul 3.
PMID: 38959304.
see also: https://www.nature.com/articles/d41586-024-02210-1
A chemical-processing technique that breaks down polyester fabrics into reusable molecules in only 15 minutes. It can even tackle mixed materials such as polycotton, breaking down the polyester and leaving the cotton to be recovered. The researchers estimate that a refined version of the process could recycle 88% of clothing worldwide.
Ex-Meta scientists debut gigantic AI protein design model.
Callaway E.
Nature. 2024 Jul 8.
doi: 10.1038/d41586-024-02214-x. Epub ahead of print.
PMID: 38982255.
An artificial intelligence model that speaks the language of proteins (EvolutionaryScale’s AI tool, called ESM3) — one of the largest yet developed for biology — has been used to create new fluorescent molecules. It was trained on more than 2.7 billion protein sequences and structures, as well as information about these proteins’ functions. The model can be used to create proteins to specifications provided by users, akin to the text spit out by chatbots such as ChatGPT.
One of the ESM-3 proteins glows as bright as a natural GFP. What makes it unusual is that it shares less than 60% of its building-block sequence with the most closely related fluorescent protein in the model’s training data. ESM-3 is one of the first biological models that allows researchers to design new proteins by simply writing down the properties and functions they want. “It’s going to be one of the AI models in biology that everybody’s paying attention to” says computational biologist Anthony Gitter.
The perfect pesticide?
Stokstad E.
Science. 2024 Jun 28;384(6703):1398-1401.
doi: 10.1126/science.adr2991. Epub 2024 Jun 27.
PMID: 38935704.
RNA-based pesticides promise to defend crops with less damage to the environment and human health than traditional poisons. By targeting the genes in specific pests, they can leave pollinators and other species unscathed. Critics say more work needs to be done to ensure that RNA-pesticides don’t harm non-target species.
Ultra-detailed brain map shows neurons that encode words’ meaning.
Reardon S.
Nature. 2024 Jul;631(8020):264.
doi: 10.1038/d41586-024-02146-6.
PMID: 38961215.
For the first time individual brain cells have been seen to respond to the essence of words. Researchers recorded the activity of around 300 neurons each in 10 people who had electrodes implanted in their brains to manage epilepsy. Only a few neurons fired for each word when the participants listened to short sentences. Words that fell into similar categories — actions food or animals — as well as words that could be associated — such as ‘duck’ and ‘egg’ — triggered similar brain activity. To an extent the researchers could determine what people were hearing by watching their neurons fire.
Flavor-switchable scaffold for cultured meat with enhanced aromatic properties.
Lee, M., Choi, W., Lee, J.M. et al.
Nat Commun 15, 5450 (2024).
https://doi.org/10.1038/s41467-024-49521-5
Lab-grown meat closer to the real thing Researchers have engineered cultured meat that, when heated, releases beefy flavours. The trick is to add compounds associated with the Maillard reaction — which creates many of the flavours in cooked food — to lab-grown muscle cells
Biggest genome ever found belongs to this odd little plant.
Kozlov M.
Nature. 2024 May 31.
doi: 10.1038/d41586-024-01567-7. Epub ahead of print.
PMID: 38822106.
A species of fork fern Tmesipteris oblanceolata has the biggest genome ever recorded. It contains 160 billion base pairs — 11 billion more than the previous record holder the flowering plant Paris japonica and 50 times more than the human genome. It’s not known why the fern evolved that way or how it accesses the relatively small proportion of DNA that is actually useful.