MP
Structural shifts in TolC facilitate Efflux-Mediated β-lactam resistance.
Kantarcioglu I, Gaszek IK, Guclu TF, Yildiz MS, Atilgan AR, Toprak E, Atilgan C.
Commun Biol. 2024 Aug 26;7(1):1051.
doi: 10.1038/s42003-024-06750-0. PMID: 39187619.
TolC = channel for antibiotics.
Here: study of TolC-mediated β-lactam drug efflux by mutagenesis / fitness measurement and MD.
Identification of general and drug-specific efflux mechanisms and key positions at TolC’s periplasmic entry.
Mutation in the Kinase Domain Alters the VEGFR2 Membrane Dynamics.
Corsini M, Ravelli C, Grillo E, Domenichini M, Mitola S.
Cells. 2024 Aug 13;13(16):1346.
doi: 10.3390/cells13161346.
PMID: 39195235.
R1051Q VEGFR2 gof mutation associated with cancer (=> ligand-independent phosphorylation => cellular signaling and growth).
Here: study how VEGFR2R1051Q affects the behavior of the WT VEGFR2 by employing quantitative FLIM/FRET and FRAP imaging.
VEGFR2WT + VEGFR2R1051Q heterodimers => altered membrane dynamics (reduced lateral motility) and smaller mobile fraction of WT on the membrane.
Basis of Glucose and Fructose Selectivity in Sugar Transport Proteins
Camilla Gottlieb Andersen, Laust Bavnhoj, Soren Brag, Jan Heiner Driller, Bjorn Panyella Pedersen
bioRxiv 2024.07.19.604285;
doi: https://doi.org/10.1101/2024.07.19.604285
Sugar Transport Proteins (STPs) = Sugar Porters that mediate H+-driven cellular uptake of glucose. selectivity determinants ?
Here: structure of A. thaliana inward occluded STP6 with glucose bound + demonstration of its role as glucose and fructose transporter.
=> the position of a single methyl group in the binding site is sufficient to shuffle glucose and fructose specificity.
! different experimental setups strongly influence kinetic transport properties !
Druglike Molecules Binding to Large Membrane Proteins: Absolute Binding Free Energy Computation.
Wang Q, Schirmer A, Paula S, Jayasinghe M.
J Phys Chem B. 2024 Aug 27.
doi: 10.1021/acs.jpcb.4c02534. Epub ahead of print.
PMID: 39189334.
”Alchemical double-decoupling method” to calculate the standard binding free energy of drug-like molecules binding to SERCA.
=> Successful determination of the binding free energy of BHQ (aligning with experimental data), but much less so with more complex analogs.
Mapping the Human Cell Surface Interactome: A Key to Decode Cell-to-Cell Communication.
Shilts J, Wright GJ.
Annu Rev Biomed Data Sci. 2024 Aug;7(1):155-177.
doi: 10.1146/annurev-biodatasci-102523-103821. Epub 2024 Jul 24.
PMID: 38723658.
Review investigating current knowledge of the human cell surface protein interactome: current state of databases and systematic technologies to assemble surface protein interactomes.
Structural basis for lipid transfer by the ATG2A-ATG9A complex.
Wang Y, Dahmane S, Ti R, Mai X, Zhu L, Carlson LA, Stjepanovic G.
Nat Struct Mol Biol. 2024 Aug 22.
doi: 10.1038/s41594-024-01376-6. Epub ahead of print.
PMID: 39174844.
Autophagy = formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy (lipid transfer and re-equilibration).
Here: cryoEM structures of human ATG2A in complex with WD-repeat protein interacting with phosphoinositides and the ATG2A-WIPI4-ATG9A complex.
MD => mechanism of lipid extraction from the donor membranes.
Conservation and specialization of the Ycf2-FtsHi chloroplast protein import motor in green algae.
K. Liang, X. Zhan, Y. Li, Y. Yang, Y. Xie, Z. Jin, X. Xu, W. Zhang, Y. Lu, S. Zhang, Y. Zou, S. Feng, J. Wu, Z. Yan,
Cell (n.d.). https://doi.org/10.1016/j.cell.2024.08.002.
Structure of the Chlamydomonas Ycf2-FtsHi complex reveals its composition and assembly.
ATP binding induces a conformational change in the ATPase domain of Ctap1.
Preprotein interacts with Ycf2-FtsHi and enhances its ATPase activity in vitro.
Ycf2-FtsHi exhibits evolutionary diversity between green algae and land plants.
Structural insights into the chloroplast protein import in land plants
Ke Liang, Zeyu Jin, Xiechao Zhan, Yuxin Li, Qikui Xu, Yanqiu Xie, Yi Yang, Shaojie Wang, Jianping Wu, Zhen Yan.
Cell, online now
https://www.cell.com/cell/abstract/S0092-8674%2824%2900894-8
Isolation of native AtYcf2-FtsHi, AtTIC, and PsTIC-Ycf2-FtsHi ultracomplex
The composition and assembly of Arabidopsis Ycf2-FtsHi and TIC complexes are revealed.
Ycf2-FtsHi poses a tilted heterohexameric motor module staying close to TIC.
An ultracomplex structure unveils the functional cooperation between TIC and Ycf2-FtsHi
High-resolution structures of the UapA purine transporter reveal unprecedented aspects of the elevator-type transport mechanism
George Broutzakis, Yiannis Pyrris, Ifigeneia Akrani, Alexander Neuhaus, Emmanuel Mikros, George Diallinas, Christos Gatsogiannis
bioRxiv 2024.08.23.609436;
doi: https://doi.org/10.1101/2024.08.23.609436
Cryo-EM structures of FL UapA transporter from Aspergillus nidulans in various IF conformations.
=> unexpected structural role of the N-tail, which interacts with key domains of UapA: clarifies the transport mechanism + suggests that the evolution of extended cytosolic tails in eukaryotic transporters may play a critical role in both trafficking and transport functions.
Structural basis of the bacterial flagellar motor rotational switching.
Tan, J., Zhang, L., Zhou, X. et al.
Cell Res (2024).
https://doi.org/10.1038/s41422-024-01017-z
Bacterial flagellar motor = bidirectional rotary nanomachine responsible for bacterial motility by rotating the flagellum. The C ring acts as a switch for changing the rotation direction.
Here: cryo-EM of the Salmonella Typhimurium C ring => 2 distinct conformations in the default counterclockwise and CheY protein-induced clockwise states.
=> the binding of CheY induces structural changes in the C ring, which triggers the switch in rotation direction.
Engineering of ATP synthase for enhancement of proton-to-ATP ratio
Hiroshi Ueno, Kiyoto Yasuda, Norie Hamaguchi-Suzuki, Riku Marui, Naruhiko Adachi, Toshiya Senda, Takeshi Murata, Hiroyuki Noji
bioRxiv 2024.08.27.609901;
doi: https://doi.org/10.1101/2024.08.27.609901
Engineering the FoF1-ATP synthase to achieve an H+/ATP ratio of 5.9 by introducing multiple peripheral stalks each bound to a proton-conducting a-subunit !
=> the engineered FoF1 complex can synthesize ATP even at low pmf, a capability beyond that of naturally occurring enzymes.
Membranes
Terrabacteria: redefining bacterial envelope diversity, biogenesis and evolution.
Beaud Benyahia B, Taib N, Beloin C, Gribaldo S.
Nat Rev Microbiol. 2024 Aug 28.
doi: 10.1038/s41579-024-01088-0. Epub ahead of print.
PMID: 39198708.
Bacterial envelope = traditionally been categorized as either Gram-positive (monoderm) or Gram-negative (diderm). Recent studies suggest that the last bacterial common ancestor had a diderm envelope, with the OM being lost multiple times in evolution, particularly within the Terrabacteria clade.
Dignificant diversity in cell envelope structures in the clade => in contradiction with the traditional G+ / G- classifications.
Here: review exploring the unique OM biogenesis systems in Terrabacteria: their diversity, phylogeny and the vast phenotypic diversity of the cell envelopes. Large deviations from the textbook examples of diderms and monoderms, challenging the classical Gram-positive–Gram-negative divide.
Highlight the OM biogenesis in Terrabacteria = novel insights into the diversity and biogenesis of the bacterial cell envelope.
Discuss the potential evolutionary steps that might have led to the multiple losses of the OM and speculate on how the very first OM might have emerged before the last bacterial common ancestor.
Prewetting couples membrane and protein phase transitions to greatly enhance coexistence in models and cells.
Yousef Bagheri, Mason Rouches, Benjamin Machta, Sarah L Veatch
bioRxiv 2024.08.26.609758;
doi: https://doi.org/10.1101/2024.08.26.609758
Biopolymer prewetting at membranes = phase transition when membranes and biopolymers are coupled.
Here: coupling of short poly-L-Lysine and poly-L-Glutamic Acid polyelectrolytes to various membranes (reconsituted membranes and in cells).
Polyelectrolyte prewetting = highly sensitive to membrane lipid composition
Protein prewetting occurs for conditions well outside those where proteins condense in the cytoplasm + the stability of prewet domains is sensitive to perturbations of plasma membrane composition and structure.
Large-area, self-healing block copolymer membranes for energy conversion.
Sproncken CCM, Liu P, Monney J, Fall WS, Pierucci C, Scholten PBV, Van Bueren B, Penedo M, Fantner GE, Wensink HH, Steiner U, Weder C, Bruns N, Mayer M, Ianiro A.
Nature. 2024 Jun;630(8018):866-871.
doi: 10.1038/s41586-024-07481-2. Epub 2024 Jun 5.
PMID: 38839964.
Majority of technologically exploiting membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. It is challenging to maximize selectivity and permeability independently. Self-assembled biological membranes are proposed to address this problem.
Here: self-assembly strategy with biomimetic block copolymer bilayers = molecularly thin, scalable and self-healing.
The fluidity of these membranes enables functionalization with molecular carriers that shuttle K+ down a concentration gradient with selectivity +++ over Na+.
=> Enables generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.
Role of lipids in the organization of tight junction.
Ikenouchi J, Shigetomi K.
Microscopy (Oxf). 2024 Aug 24:dfae039.
doi: 10.1093/jmicro/dfae039. Epub ahead of print.
PMID: 39185601.
Phase separation of lipids and liquid-liquid phase separation of proteins are important driving forces for self-assembly of cell adhesion structures.
Here: review summarizing recent findings on the role of lipids as scaffolds for supramolecular complexes, using tight junctions in epithelial cells as an example.
Melittin can permeabilize membranes via large transient pores.
Ulmschneider JP, Ulmschneider MB.
Nat Commun. 2024 Aug 23;15(1):7281.
doi: 10.1038/s41467-024-51691-1.
PMID: 39179607
Membrane active peptides can create pores in lipid bilayers, but permeabilization mechanisms have been challenging to determine experimentally.
Here: MD to study equilibrium poration and transient leakage for peptides (alamethicin and melittin) => detailed pore structures and mechanisms, with high agreement with experimental data.
Tensing Flipper: Photosensitized Manipulation of Membrane Tension, Lipid Phase Separation, and Raft Protein Sorting in Biological Membranes.
Torra J, Campelo F, Garcia-Parajo MF.
J Am Chem Soc. 2024 Aug 28;146(34):24114-24124.
doi: 10.1021/jacs.4c08580. Epub 2024 Aug 20.
PMID: 39162019.
Lipid rafts modulate the properties of membranes and drive protein sorting.
Here: unidentified property of Flipper (a commercially available fluorescent membrane tension probe) = ability to photosensitize singlet oxygen under blue light when embedded into lipid membranes => production of lipid hydroperoxides that increase membrane tension and trigger phase separation.
In biological membranes, the photoinduced segregated domains retain the sorting ability of intact phase-separated membranes, directing raft and nonraft proteins into ordered and disordered regions, respectively, in contrast to radical-based photo-oxidation reactions that disrupt raft protein partitioning.
Microbio
Downregulation of Klebsiella pneumoniae RND efflux pump genes following indole signal produced by Escherichia coli.
Salama GG, El-Mahdy TS, Moustafa WH, Emara M.
BMC Microbiol. 2024 Aug 24;24(1):312.
doi: 10.1186/s12866-024-03443-w.
PMID: 39182027.
Biological roles of indole (produced by many bacteria) => significant impact on the virulence of non-indole-producing bacteria, such as P. aeruginosa, Proteus mirabilis, and K. pneumoniae, particularly in mixed infections with Escherichia coli.
Here: indole can reduce atbR in these bacteria, influence biofilm production, and decrease the expression of efflux pump genes.
Miscellaneous
Measuring the Surface Tension of Atmospheric Particles and Relevant Mixtures to Better Understand Key Atmospheric Processes.
El Haber M, Gérard V, Kleinheins J, Ferronato C, Nozière B.
Chem Rev. 2024 Aug 23.
doi: 10.1021/acs.chemrev.4c00173. Epub ahead of print.
PMID: 39177157.
The surface tension of atmospheric particles can affect their size distribution, condensational growth, evaporation, and exchange of chemicals with the atmosphere (= important in geochemical processes).
Review presenting experimental approaches + inventory of experimental adsorption isotherms for over 130 mixtures of organic compounds in water of relevance for model development and validation +potential future areas of research.
What accelerates brain ageing? This AI ‘brain clock’ points to answers.
Nowogrodzki J.
Nature. 2024 Aug 27.
doi: 10.1038/d41586-024-02770-2. Epub ahead of print.
PMID: 39192079.
“The way your brain ages, it’s not just about years. It’s about where you live, what you do,” says neuroscientist Agustín Ibáñez. He is co-author on a new study that looked at ‘brain-age gaps’ — whether a person’s brain is ageing faster than their chronological age would suggest. The researchers assessed a complex form of functional connectivity, a measure of the extent to which brain regions are interacting with one another, which generally declines with age. Structural socioeconomic inequality, exposure to air pollution and health disparities were linked to larger brain-age gaps, especially in people from Latin America.
Humanity’s newest brain gains are most at risk from ageing.
Mallapaty S.
Nature. 2024 Aug 29.
doi: 10.1038/d41586-024-02784-w. Epub ahead of print.
PMID: 39198613.
Regions of the human brain that are the last to mature, such as parts of the frontal lobe, are the first to show signs of ageing, a theory known as ‘last in, first out’. New research shows that some of these regions are also the ones that evolved most recently — those linked to decision-making and self-control. The results tend to support the “important hypothesis that our cortical expansion came at the price of age-related decline”, says neuroscientist Rogier Mars.
Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome.
Carlino N et al.,
Cell. 2024 Aug 16:S0092-8674(24)00833-X.
doi: 10.1016/j.cell.2024.07.039. Epub ahead of print.
PMID: 39214080.
Scientists sequenced microbial DNA from nearly 2000 foods including fermented favourites such as Gorgonzola cheese sauerkraut kefir and kimchi. About half the microbes the researchers identified were new. Pulque — a sour agave wine drunk in Mexico — was especially rich in this microbial dark matter as were African palm wine and cheese brine. And a small percentage of people’s gut microbiome matched what was found in food — either because of what they ate or because of some instance in the past when food microbes became established in peoples’ guts.
Denebian Glamour’s what’s hot and what’s not for the next millennium.
Lingen M.
Nature. 2024 Aug 28.
doi: 10.1038/d41586-024-02766-y. Epub ahead of print.
PMID: 39198608.
Hot or not ?
All you need to know on the latest trends across the Galaxy!
Fish can tell the direction of sounds – here’s how.
Bates E.
Nature. 2024 Jul 31.
doi: 10.1038/d41586-024-02518-y. Epub ahead of print.
PMID: 39085638.
https://youtu.be/PN6RpwMZJCU