MP
Cryo-EM structure of the Mycobacterium smegmatis MmpL5-AcpM complex.
Maharjan R, Zhang Z, Klenotic PA, Gregor WD, Purdy GE, Yu EW.
mBio. 2024 Dec 11;15(12):e0303524.
doi: 10.1128/mbio.03035-24. Epub 2024 Oct 31.
PMID: 39480109.
1st structure of MmpL5 (essential transporter for iron acquisition), bound with the meromycolate extension acyl carrier protein M (AcpM) => plausible pathway for mycobactin translocation.
Rapid kinetics of H+ transport by membrane pyrophosphatase: Evidence for a “direct-coupling” mechanism.
Anashkin VA, Bogachev AV, Serebryakova MV, Zavyalova EG, Bertsova YV, Baykov AA.
Biochem Biophys Res Commun. 2024 Dec 19;744:151203.
doi: 10.1016/j.bbrc.2024.151203. Epub ahead of print.
PMID: 39708396.
Stress-resistance membrane pyrophosphatase (mPPase) = proton pump found in microbes and plants that couples pyrophosphate hydrolysis with H⁺ transport out of the cytoplasm.
Here: using a stopped-flow pyranine assay, authors show that H⁺ transport in mPPase-containing vesicles occurs upon pyrophosphate hydrolysis, not mere binding. This contradicts the “pumping-before-hydrolysis” model.
Distinctive roles of aquaporins and novel therapeutic opportunities against cancer.
Yadav DK Singh DD Shin D.RSC Med Chem. 2024 Dec 17.
doi: 10.1039/d4md00786g. Online ahead of print.
PMID: 39697243.
AQPs play critical roles in both normal physiology and cancer progression, particularly in highly metastatic tumors where AQP expression is elevated.
Recent research showed AQPs’ contributions to oncogenic processes (cell migration, proliferation, …) => they are promising but challenging targets for anticancer therapy.
Advances in AQP-targeted strategies, such as monoclonal antibodies against aquaporin-4 in glioblastoma, offer hope for selective and effective cancer treatments, with future research focusing on overcoming challenges in inhibitor development and exploring novel therapeutic avenues.
Quaternary arrangements of membrane proteins: an aquaporin case.
Hrmova M.
Biochem Soc Trans. 2024 Dec 13:BST20241630.
doi: 10.1042/BST20241630. Online ahead of print.
PMID: 39670669.
Mini-review highlighting factors influencing transporter integration in membranes, focusing on AQP tetramer formation and lipid interactions in bacterial and mammalian membranes.
Insights into substrate recognition and export tunnel preferences in the efflux transporter AcrB.
Makhamadjamonov F Karolak ME Smyth L Ababou A.
Protein Sci. 2025 Jan34(1):e5252.
doi: 10.1002/pro.5252.
PMID: 39673478
AcrB uses 3 distinct export tunnels for substrate extrusion.
Here: gate loop mutations revealed that conformational change kinetics, rather than direct molecular interactions, influence substrate export and tunnel preference, which varies even among structurally similar substrates.
Identifying optimal substrate classes of membrane transporters.
Denger A Helms V.
PLoS One. 2024 Dec 1919(12):e0315330.
doi: 10.1371/journal.pone.0315330. eCollection 2024.
PMID: 39700222.
Identifying MP transporters along with their substrates is vital for fields like biotechnology and pharmacology.
Here: to address the complexity and redundancy in functional annotations for supervised learning, researchers developed an automated pipeline using ML to select a subset of functional annotations that are non-redundant, separable, and relevant to substrate transport.
Substrate Uptake by TonB-Dependent Outer Membrane Transporters.
Braun V.
Mol Microbiol. 2024 Dec122(6):929-947.
doi: 10.1111/mmi.15332. Epub 2024 Dec 3.
PMID: 39626085.
Review on the critical role of TBDTs in bacterial survival and pathogenesis. TonB binds to the conserved TonB box in TBDTs, transmitting energy from the pmf via the ExbB-ExbD complex to induce structural changes that open the pores and enable substrate translocation. This system supports the import of diverse substrates, including nutrients and toxins.
Dynamic interplay between a TonB-dependent heme transporter and a TonB protein in a membrane environment.
Somboon K, Melling O, Lejeune M, Pinheiro GMS, Paquelin A, Bardiaux B, Nilges M, Delepelaire P, Khalid S, Izadi-Pruneyre N.
mBio. 2024 Dec 11;15(12):e0178124.
doi: 10.1128/mbio.01781-24. Epub 2024 Oct 30.
PMID: 39475239.
MS of the E. coli envelope => dynamic interactions between the OM heme transporter HasR and the IM TonB-like protein HasB, crucial for transferring pmf energy for heme uptake.
These simulations identify a novel network of HasR-HasB interactions within the periplasm, are validated experimentally, and suggest that similar mechanisms may exist in other nutrient import systems.
The C-terminal α-helix is crucial for the activity of the bacterial ABC transporter BmrA.
Osten V Oepen K Schneider D.
J Biol Chem. 2024 Dec 18:108098.
doi: 10.1016/j.jbc.2024.108098.
PMID: 39706270.
Deletion of C-terminal α-helix of Bacillus subtilis BmrA abolishes function, while specific residues within its N-terminal segment are critical, likely due to ATP recognition and hydrolysis. In contrast, the very C-terminal fragment exhibits high flexibility and is not crucial for BmrA activity.
YibN, a bona fide interactor of YidC with implications in membrane protein insertion and membrane lipid production
Zhiyu Zhao, Nachi Yamamoto, John Young, Nestor Solis, Amos Fong, Mohammed Al-Seragi, Sungyoung Kim, Hiroyuki Aoki, Sadhna Phanse, Hai-Tuong Le, Christopher Overall, Hanako Nishikawa, Mohan Babu, Ken-ichi Nishiyama, and Franck Duong
bioRxiv posted 14 December 2024
doi:10.1101/2024.12.13.628402
YidC = essential for bacterial IM biogenesis, interacting with the Sec translocon for multi-pass MP folding + independently functioning as an insertase and lipid scramblase.
Here: using BioID, YibN was identified as a critical component of the YidC protein environment + role in enhancing the insertion and production of YidC substrates and promoting IM proliferation.
Membrane
Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria.
Mu A, et al.
Nat Commun. 2023 Mar 18;14(1):1530.
doi: 10.1038/s41467-023-37200-w.
PMID: 36934086.
Comprehensive genomic, transcriptomic, proteomic, and metabolomic framework was applied to clinical isolates of four major sepsis-causing pathogens (E. coli, K. pneumoniae, SA and S. pyogenes).
Exposure to human serum => sepsis-specific molecular signature, highlighting increases in fatty acid and lipid biosynthesis, cell envelope remodelling, and nutrient adaptation.
!!! Acquisition of cholesterol was identified across the bacterial species !!!
Lipid Flipping, O-antigen Shielding, and Water Dynamics Revealed by 100-200 µs Coarse-Grained Simulations of E. coli Outer Membrane Proteins
Andrew Kalenkiewicz, Adrian H. Elcock
bioRxiv 2024.12.09.627556;
doi: https://doi.org/10.1101/2024.12.09.627556.
CG MD with the Martini3 FF, => model of 10 E. coli OMPs in different OM models, revealing OMP-phospholipid interactions and the novel ability of OMPs to facilitate phospholipid flipping.
- study shows that longer LPS O-antigen chains occlude OMPs
- detailed analysis of water and ion movement across the OM.
Galactocerebroside Lipid Nanotubes a Model Membrane System for Studying Membrane-Associated Proteins on a Molecular Scale.
Di Cicco A Manzi J Maufront J Cheng X Dezi M Lévy D.
Methods Mol Biol. 20252888:237-248.
doi: 10.1007/978-1-0716-4318-1_16.
PMID: 39699735.
Galactocerebroside lipid nanotubes = membrane-mimicking systems for studying proteins involved in membrane shape remodeling.
They have constant and small diameter of 30 nm and a length of up to 2 μm and can be functionalized with lipid ligands.
(p)ppGpp Buffers Cell Division When Membrane Fluidity Decreases in Escherichia coli.
Singh V Harinarayanan R.
Mol Microbiol. 2024 Dec122(6):847-865.
doi: 10.1111/mmi.15323. Epub 2024 Oct 26.
PMID: 39461000.
Fluidity of bacterial membranes = crucial for membrane-associated processes.
Regulation through temperature and unsaturated fatty acid content is essential for maintaining optimal function.
Here: strains deficient in (p)ppGpp and FadR (fatty acid metabolism regulator) exhibit growth defects, which are rescued by increasing growth temperature or unsaturated fatty acid content.
- (p)ppGpp regulates cell division during membrane fluidity loss by enhancing FtsZ => first report of (p)ppGpp-mediated adaptation to membrane fluidity changes in bacteria.
Assessing the interaction between the N-terminal region of the membrane protein magnesium transporter A and a lipid bilayer.
Skog AE Jones NC Månsson LK Morth JP Vrønning Hoffmann S Gerelli Y Skepö M.
J Colloid Interface Sci. 2024 Dec 16683(Pt 1):663-674.
doi: 10.1016/j.jcis.2024.12.064.
PMID: 39706085.
Interaction of KEIF (IDR N-terminal region of MgtA), with lipid bilayers mimicking cell membranes.
Combining experimental techniques (neutron reflectometry, QCM-D, SRCD, and oriented CD) with MD.
=> KEIF undergoes a transition from a disordered to a structured α-helical state upon adsorption to lipid bilayers, where it resides in the hydrophobic tail region, with electrostatic interactions influenced by bilayer charge and ionic strength, potentially modulating MgtA function in the plasma membrane.
Molecules
Characterization of intact FeoB in a lipid bilayer using styrene-maleic acid (SMA) copolymers.
Lee M Armstrong CM Smith AT.
Biochim Biophys Acta Biomembr. 2024 Dec 16:184404.
doi: 10.1016/j.bbamem.2024.184404. Online ahead of print.
PMID: 39694085.
Fe2+ = vital for pathogenic bacteria like Vibrio cholerae, which uses the Feo system for iron uptake (cytosolic proteins + transmembrane FeoB).
Here: SMA copolymers to isolate and study V. cholerae FeoB in lipid particles.
=> VcFeoB is mostly monomeric in a lipid bilayer and shows enhanced NTPase activity compared to detergent micelles.
Methods
Protocol for purifying and reconstituting a vacuole membrane transporter Ypq1 into proteoliposomes.
Arines FM, Wielenga A, Stockbridge RB, Li M.
STAR Protoc. 2024 Dec 10;5(4):103483.
doi: 10.1016/j.xpro.2024.103483. Epub ahead of print.
PMID: 39661504.
Protocol for overexpressing, purifying, and reconstituting a vacuole membrane transporter Ypq1 into proteoliposomes and steps to measure transport activity using radioactive substrates.
Effect of Exogenous Glucose on Molecular Transport through Bacterial Membranes Studied by Second Harmonic Light Scattering.
Hu XH, Li Y, Wu T, Ma J, Wu Y, Wilhelm MJ, Dai HL.
J Phys Chem B. 2024 Dec 19;128(50):12379-12388.
doi: 10.1021/acs.jpcb.4c06134. Epub 2024 Dec 11.
PMID: 39659191.
Exogenous glucose increases the efficacy of AGs in eliminating bacterial persister cells: increased antimicrobial efficacy induced by glucose-facilitated uptake of the antibiotics ?
Here: second-harmonic light scattering to time-resolve the transport of an antimicrobial quaternary ammonium compound across the membranes of living E. coli in the presence of glucose.
=> low concentration glucose enhances the uptake of antimicrobials into the bacteria => improvement of antimicrobial efficacy.
Cryo-electron tomography: en route to the molecular anatomy of organisms and tissues.
Schiøtz OH, Klumpe S, Plitzko JM, Kaiser CJO.
Biochem Soc Trans. 2024 Dec 19;52(6):2415-2425.
doi: 10.1042/BST20240173.
PMID: 39641594.
Recent developments towards ”molecular anatomy” (sic) studies using cryo-ET, and brief outlines what can be expected in the near future.
Minimizing ice contamination during specimen preparation for cryo-soft X-ray tomography and cryo-electron tomography.
C.-C. Hsieh, Z.-J. Lin, and L.-J. Lai.
Journal of Structural Biology: X, vol. 10, p. 100113, 2024.
Cryo-soft X-ray tomography (cryo-SXT) = technique used to image 3D whole cells in nearly native states. It requires efficient cryo-sample grid preparation to avoid ice contamination.
Here: introduction of a cryo-multi-grid-box storage system that enhances grid storage, reduces grid transfers, and minimizes ice formation, improving the sample preparation process.
Monitoring conformational changes in the human neurotransmitter transporter homologue LeuT with 19F-NMR spectroscopy.
Daminato A Loland CJ Cabrita EJ.
J Neurochem. 2025 Jan169(1):e16278.
doi: 10.1111/jnc.16278.
PMID: 39680492.
Neurotransmitter:sodium symporters (NSS) are thought to work via the alternating access mechanism, exploring multiple configurations dictated by the binding of substrates and ions.
Dynamical data connecting the already published crystal structure to the transport cycle are critical to understanding how ligands are translated through the membrane.
Here: 19F-based NMR spectroscopy to monitor how substrates and ions binding affect the conformations of the transporter.
Na+ ions produce closure of the extracellular vestibule to a state similarly induced by Na+ and substrates.
K+ ions seem to shift the conformational equilibrium toward IF intermediates (=> competing with Na+).
Comprehensive microcrystal electron diffraction sample preparation for cryo-EM.
Nicolas WJ Gillman C Weaver SJ Clabbers MTB Shiriaeva A Her AS Martynowycz MW Gonen T.
Nat Protoc. 2024 Dec 20.
doi: 10.1038/s41596-024-01088-7.
PMID: 39706914.
MicroED = cryogenic electron microscopy technique used for determining the structures of small crystals, including proteins, by rotating them in an electron beam while capturing diffraction data.
Here: detailed instructions and optimization strategies for MicroED sample preparation.
Microbio
Natural Inhibitors of Salmonella MDR Efflux Pumps AcrAB and AcrD: An Integrated In Silico Molecular and In Vitro Investigation.
El-Demerdash AS Kamel SA Elariny EYT Henidi H Mahran Y Alahdal H Saleh AM Ibrahim RA.
Int J Mol Sci. 2024 Dec 225(23):12949.
doi: 10.3390/ijms252312949.
PMID: 39684663.
Study of the potential of essential oil components as EPIs of AcrAB and AcrD from Salmonella efflux.
Cumin and cinnamon oils => significant inhibition, with molecular docking simulations revealing strong binding affinities and higher stability within the AcrAB and AcrD binding pockets.
Treatment with these oils also downregulated EP gene expression.
Mito
Prohibitin 1 tethers lipid membranes and regulates OPA1-mediated membrane fusion.
Ban T Kuroda K Nishigori M Yamashita K Ohta K Koshiba T.
J Biol Chem. 2024 Dec 13:108076.
doi: 10.1016/j.jbc.2024.108076. Online ahead of print.
PMID: 39675719
Prohibitins (PHBs), expressed in the mitochondrial IM = scaffolds for mitochondrial proteins and PL, with PHB1 playing a critical role in regulating mitochondrial dynamics and integrity.
Here: characterization of the biophysical properties of recombinant PHB1, revealing its oligomerization via a coiled-coil region, which is essential for mitochondrial morphology and membrane fusion.
PHB1 facilitates fusion through OPA1.
Miscellaneous
The best science images of 2024 — Nature’s picks
Nature 13 December 2024.
Text by Nisha Gaind and Emma Stoye.
The year brought surreal developments in robotics, stunning auroras and feats that pushed the limits of biology. These are Nature’s picks of the year’s best science images. A breathtaking total eclipse, courageous penguins, volcanic smoke rings and more.
Creating ‘Mirror Life’ Could Be Disastrous, Scientists Warn
Simon Makin
Scientific American
Dec 14, 2024
Scientists are warning of the dangers of synthetic organisms in which the ‘handedness’ of life is reversed from its normal flow (in which DNA and RNA are made from ‘right-handed’ nucleotides, and proteins are made from ‘left-handed’ amino acids). A group of 38 researchers warn that such mirror-universe bacteria might be able to evade immune systems and predators such as phages running riot in ecosystems and causing deadly infections. Others are not so concerned.
‘Getting paid to review is justice’: journal pays peer reviewers in cryptocurrency.
Else H.
Nature. 2024 Dec 11.
doi: 10.1038/d41586-024-04027-4. Epub ahead of print.
PMID: 39663443.
ResearchHub Journal launches latest attempt to compensate referees for their labour.
Controversial COVID study that promoted unproven treatment retracted after four-year saga.
Van Noorden R.
Nature. 2024 Dec 18.
doi: 10.1038/d41586-024-04014-9. Epub ahead of print.
PMID: 39695288.
Paper on hydroxychloroquine is second-most-cited study ever to be withdrawn.
Diatom phytochromes integrate the underwater light spectrum to sense depth.
Duchêne C, Bouly JP, Pierella Karlusich JJ, Vernay E, Sellés J, Bailleul B, Bowler C, Ribera d’Alcalà M, Falciatore A, Jaubert M.
Nature. 2024 Dec 18.
doi: 10.1038/s41586-024-08301-3. Epub ahead of print.
PMID: 39695224.
Study explorin how diatom phytochromephotoreceptors (DPH) perceive changes in light spectra with depth in aquatic environments. DPH regulates photosynthesis acclimation under low-blue-light conditions, linking light detection with functional response.
=> suggests that DPH helps diatoms adapt to vertical displacements in the water column, offering a new perspective on how aquatic organisms use light cues to modulate their physiology.
Congrats Angela and colleagues !