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The role of ABC transporter DrrABC in the export of PDIM in Mycobacterium tuberculosis.

Nabiela Moolla, Helen Weaver, Rebeca Bailo, Albel Singh, Vassiliy N. Bavro, Apoorva Bhatt.

The Cell Surface, Volume 12,2024,

100132,

ISSN 2468-2330,

https://doi.org/10.1016/j.tcsw.2024.100132.

Export of the virulence lipid PDIM in Mycobacterium tuberculosis relies on a complex system MmpL7, the lipoprotein LppX, and an DrrA, DrrB, and DrrC (= complex ABC transporters). 

Any of the drr genes deleted => PDIM export fails completely. 

Here: bioinformatic analysis and mutagenesis => the DrrABC complex is identified as a Type V ABC transporter with unique structural features, including a specialized C-terminal domain in DrrA that may contribute to its function.

 

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 Oct 30:e0178124. 

doi: 10.1128/mbio.01781-24. Epub ahead of print. 

PMID: 39475239.

Exact molecular mechanism of TonB-dependent transport is unclear due to incomplete structural data and challenges in studying this flexible, multicomponent system. 

Here: combination of advanced MD with microbiology and biochemical experiments to enhance our understanding of the molecular interactions.
 
 

Cryo-EM structures of the zinc transporters ZnT3 and ZnT4 provide insights into their transport mechanisms. 

Ishida H, Yo R, Zhang Z, Shimizu T, Ohto U.

FEBS Lett. 2024 Oct 30. 

doi: 10.1002/1873-3468.15047. Epub ahead of print. 

PMID: 39474773.

Zinc transporters (ZnTs) = H⁺/Zn²⁺ antiporters.

ZnT3 transport Zn²⁺ into synaptic vesicles for neurotransmission.

ZnT4 direct Zn²⁺ into lysosomes to reduce cell injury. 

Here: cryoEM structures of human ZnT3 and ZnT4 (ZnT3 in IF and ZnT4 in OF).

=> insights into the conformational changes involved in the Zn²⁺ transport.

 

Structure, dynamics and evolution of the Candida albicans multi-drug resistance ABC transporter CDR1

Jeeeun Shin, Ruitao Jin, Barnabas Gall, Chacko Jobichen, Colin J Jackson, Melanie Rug, Ben Corry, Joseph Brock

bioRxiv 2024.10.28.620768; 

doi: https://doi.org/10.1101/2024.10.28.620768 

High-resolution cryoEM=> structures of CDR1 in various functional states (nucleotide-bound, substrate-bound, and apo forms) + Cdr1 bound to substrates like rhodamine 6G and Oregon Green 488. 

=> asymmetric nucleotide-binding sites (NBS): ATP binds to the deviant NBS1 and ADP to the canonical NBS2 => conformational changes necessary for substrate transport. 

MD + evolutionary analysis => key functional motifs and potential resistance-associated variations.

 

The effect of oxidative stress on the Adenosine A2a Receptor structure, activity and signalling

Idoia Company, Joseph Gunner, David R Poyner, John Simms, Andrew R Pitt, Corinne M Spickett

bioRxiv 2024.10.31.620957; 

doi: https://doi.org/10.1101/2024.10.31.620957 

A2aR = GPCR with anti-inflammatory effects. 

Here: using SMA to retain membrane lipids, authors found that oxidative stress did not alter A2aR’s ligand-induced conformational changes in isolated samples. However, in HEK293 cells, oxidative stress increased cAMP production in response to an agonist.

=> oxidative stress helps regulate inflammation via the A2aR signaling pathway ?
 

 

Membranes

 

Lipid Demixing Reduces Energy Barriers for High Curvature Vesicle Budding

Itay Schachter

bioRxiv 2024.10.24.620077; 

doi: https://doi.org/10.1101/2024.10.24.620077 

Budding relies on asymmetries (differences in leaflet composition, area, and osmotic conditions) and involves large curvature changes in lipid vesicles. So far, the combined impact of asymmetry and high curvatures on budding has remained unknown. 

Here: using continuum elastic theory, the budding pathway is detailed. 

=> quantitative description of the budding process and the budded state of both ideally and non-ideally mixed lipid nanoscale vesicles: budding is less favored in smaller vesicles but lipid demixing can significantly reduce its energy barrier.

 

Methods

SMARTINI3 parametrization of multi-scale membrane models via unsupervised learning methods. 

Soleimani A, Risselada HJ.

Sci Rep. 2024 Oct 28;14(1):25714. 

doi: 10.1038/s41598-024-75490-2. 

PMID: 39468134.

Development of an ultra-coarse-grained (ultra-CG) membrane model, SMARTINI3 (compatible with GROMACS simulation software). The model is parameterized to accurately replicate the properties of PC membranes + successfully reproduces the behavior of TM domains within lipid bilayers.

 

Triple labeling resolves a GPCR intermediate state by 3-color single molecule FRET

Leo Bonhomme, Ecenaz Bilgen, Caroline Clerté, Jean-Philippe Pin, Philippe Rondard, Emmanuel Margeat, Don C. Lamb, Robert B. Quast

bioRxiv 2024.10.31.621373; 

doi: https://doi.org/10.1101/2024.10.31.621373 

Novel orthogonal triple-labeling strategy for single molecule FRET => three simultaneous distance measurements with high temporal resolution by using genetically encoded non-canonical amino acids and an enzymatic self-labeling SNAP tag. 

Method successfully applied to the human metabotropic glutamate receptor 2.

 

Calculation of minimum energy pathways in transport proteins.

Briony A Yorke, Helen M Ginn

bioRxiv 2024.08.07.607056; 

doi: https://doi.org/10.1101/2024.08.07.607056 

Transitions between protein metastable states are hard to capture experimentally.

Here: new algorithm = “cold-inbetweening” algorithm to simulate shifts in torsion angle space, minimizing kinetic energy between known end-states. 

Applied to 3 MPs (DraNramp, MalT, and MATE) =>revealing distinct conformational changes supporting the alternate access model + specific structural shifts (unwinding of support helices or helix rewinding).

 

Microbio

Quantifying bacterial efflux within subcellular domains of Pseudomonas aeruginosa. 

Li Y, Wilhelm MJ, Wu T, Hu X-H, Ruiz ON, Dai H-L.

Appl Environ Microbiol. 2024 Oct 30:e0144724. 

doi: 10.1128/aem.01447-24. Epub ahead of print. 

PMID: 39475289.

Knowledge of the influence of efflux in individual subcellular domains and the associated ejection rates is still lacking. 

Here: using the nonlinear optical technique, second-harmonic light scattering, authors measured the threshold concentrations for pump activation, saturation concentrations, and efflux rates from both the periplasm and cytosol in living Gram-negative bacteria. 

 

Cell polarity control by an unconventional G-protein complex in bacteria

Tâm Mignot, Céline Dinet, Corinne Kreuzer, Deborah Byrne, Sébastien Lhospice, Julien Herrou, Fabien Durbesson, Renaud Vincentelli, Alphée Michelot

bioRxiv 2024.10.31.621274; 

doi: https://doi.org/10.1101/2024.10.31.621274 

In Myxococcus xanthus, cell polarity and motility are regulated by the small GTPase MglA and its regulators, MglB and the RomRX complex. 

Here: study reveals that:

  • RomRX acts as an effector that specifically binds to MglA-GTP rather than functioning as a guanine nucleotide exchange factor (GEF) 
  • MglB is shown to be a weak catalyst that requires other factors to dissociate from MglA. 

RomR competes with MglA for MglB => enables GAP activity while effectively partitioning these proteins within the cell. 

 

Miscellaneous

Parallel molecular data storage by printing epigenetic bits on DNA. 

Zhang C, Wu R, Sun F, Lin Y, Liang Y, Teng J, Liu N, Ouyang Q, Qian L, Yan H.

Nature. 2024 Oct;634(8035):824-832. 

doi: 10.1038/s41586-024-08040-5. Epub 2024 Oct 23. 

PMID: 39443776.

DNA storage = potential to transcend current data storage technologies but writing large-scale data directly into DNA sequences is timely and costly. 

Here: alternative strategy => writing of arbitrary data on DNA using premade nucleic acids with methylation as information bits = molecular movable-type printing. 

=> writing of approximately 275,000 bits on an automated platform with 350 bits written per reaction. The data encoded were HT retrieved by nanopore sequencing, and algorithms were developed to finely resolve 240 modification patterns per sequencing reaction. 

 

The huge protein database that spawned AlphaFold and biology’s AI revolution. 

Callaway E.

Nature. 2024 Oct;634(8036):1028-1029. 

doi: 10.1038/d41586-024-03423-0. 

PMID: 39424937.

No PDB, no AF !

 

Will AI’s huge energy demands spur a nuclear renaissance? 

Castelvecchi D.

Nature. 2024 Oct 25. 

doi: 10.1038/d41586-024-03490-3. Epub ahead of print. 

PMID: 39455831.

Energy requirement of data centres supporting artificial intelligence (AI) skyrockets.

Tech giants recently announced plans to support nuclear power generation to become carbon-neutral: design of ‘small modular reactors’ or support for the restart of a decommissioned 835-megawatt reactor in Pennsylvania.

 

Far-right governments seek to cut billions of euros from research in Europe. 

Matthews D.

Nature. 2024 Oct 28. 

doi: 10.1038/d41586-024-03506-y. Epub ahead of print. 

PMID: 39468345.

A surge in far-right parties entering governments across Europe is raising concerns for science. Policy experts warn that these parties typically show no interest in research and innovation, leaving scientists vulnerable to budget cuts. In the Netherlands, researchers are bracing for €1 billion in cuts to the university and research budget under a coalition government including the anti-Islam Party for Freedom. 

The coalition also wants to limit the intake of international students and implement rules that would require universities to apply for permission to teach courses in English, which could trigger an exodus of foreign academics who don’t want to, or can’t, teach in Dutch.  

 

Scare tactics: scientists offer insights on what makes a perfect prank

The Guardian

Linda Geddes

Wed 30 Oct 2024 12.23 CET

https://www.theguardian.com/science/2024/oct/30/scare-tactics-scientists-offer-insights-on-what-makes-a-perfect-prank?CMP=share_btn_url

 

“Don’t dress up like a serial killer and hide in your grandmother’s closet, but don’t just walk up to your friend and say: ‘boo’, either.” Planning a Halloween scare? Take some advice from humour researcher Marc Hye-Knudsen. Pranks should be scary enough that it violates the subject’s expectations, but not so scary that they can’t laugh about it afterward.