MP
The structures of the peptide transporters SLC15A3 and SLC15A4 reveal the recognition mechanisms for substrate and TASL.
Zhang Z Kasai S Sakaniwa K Fujimura A Ohto U Shimizu T.
Structure. 2024 Dec 13:S0969-2126(24)00532-X.
doi: 10.1016/j.str.2024.11.019. Online ahead of print.
PMID: 39719710.
SLC15A3 and SLC15A4 = endolysosomal transporters that move histidine and dipeptides into the cytosol (SLC15A4 is also scaffold for TASL recruitment).
Here: cryo-EM structures => outward-facing conformations, substrate recognition mechanism, and TASL interaction.
Cryo-EM structure of the human Pannexin-3 channel.
Tsuyama T Teramura R Mitsuoka K Kishikawa JI Yokoyama K.
Biochem Biophys Res Commun. 2024 Dec 20745:151227.
doi: 10.1016/j.bbrc.2024.151227. Online ahead of print.
PMID: 39721314.
Pannexin-3= heptameric ATP-permeable channel involved in developmental and pathological processes through ATP and Ca²⁺ ion permeation.
Here: cryo-EM structures=> TM pore with an isoleucine ring as its narrowest constriction and dynamic intracellular regions.
Deciphering the molecular basis of lipoprotein recognition and transport by LolCDE.
Qiao W Shen C Chen Y Chang S Wang X Yang L Pang J Luo Q Zhang Z Xiang Y Zhao C Lu G Ding BS Ying B Tang X Dong H.
Signal Transduct Target Ther. 2024 Dec 279(1):354.
doi: 10.1038/s41392-024-02067-w.
PMID: 39725716.
Structural and functional studies of LolCDE ABC transporter => the N-terminal linker of lipoproteins plays a key role in substrate binding, while specific residues mediate allosteric communication for lipoprotein relocation.
Investigation of Transient Temperature Rising of Light-Harvesting Complex II by Nonradiative Heat Dissipation at the Protein Level.
Ruan M Xu Y Liao G Wang Z Chen H Weng Y.
J Phys Chem Lett. 2024 Dec 26:308-316.
doi: 10.1021/acs.jpclett.4c03056. Online ahead of print.
PMID: 39723969.
LHCII captures light energy under low light and dissipates excess energy as heat under high light.
Here: using time-resolved pump-probe spectroscopy, authors describe a transient temperature rise and conformational changes in LHCII induced by excited-state heat dissipation, confirming a temperature increase consistent with theoretical predictions.
=> dual protective and energy-harvesting roles by LHCII.
Bioengineered yeast tethered respiratory supercomplexes reveal mechanisms governing efficient substrate utilization.
Mazzen H Eldeeb, Zoe Cosner, Andreas Carlstrom, Jeffri-Noelle Mays, Gabriella F Rodriguez, Jens Berndtsson, Martin Ott, and Flavia Fontanesi.
bioRxiv posted 21 December 2024.
doi:10.1101/2024.12.19.629262
Mitochondrial respiratory chain supercomplexes (SCs), such as III2IV1 and III2IV2 in yeast, play a crucial role in facilitating cytochrome c diffusion and enhancing respiratory efficiency.
Here: engineering of a yeast strain expressing a covalently linked III2IV2 SC.
=> SC organization selectively impacts mitochondrial respiration of cytosolic NADH, likely due to specific interactions with NADH dehydrogenases.
=> Suggest that substrate-driven SC configurations optimize electron flux and contribute to metabolic flexibility.
Membranes
Membranes are functionalized by a proteolipid code.
Kervin TA, Overduin M.
BMC Biol. 2024 Feb 27;22(1):46.
doi: 10.1186/s12915-024-01849-6.
PMID: 38414038.
Membranes are proposed to be organized into structural and functional zones like receptor clusters and cell junctions.
Here: a protein-lipid code is suggested to govern the assembly of these zones, opposing the idea that lipids independently sort proteins into stable regions. This model emphasizes the interplay between proteins and lipids in structuring membrane domains.
Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft Partitioning.
Stefanski KM, Huang H, Luu DD, Hutchison JM, Saksena N, Fisch AJ, Hasaka TP, Bauer JA, Kenworthy AK, Van Horn WD, Sanders CR.
bioRxiv [Preprint]. 2024 Dec 11:2024.10.28.620521.
doi: 10.1101/2024.10.28.620521.
PMID: 39713458.
Identification of small molecules that modulate the association of peripheral myelin protein 22 with lipid rafts in plasma membrane vesicles.
Two compound classes: class I alters raft protein affinity and reduces raft formation in a protein-dependent manner / class II affects raft formation independently of proteins. Both classes influence membrane fluidity and TRPM8 channel function.
Lipid Bilayer Strengthens the Cooperative Network of Membrane Proteins.
Shaima Muhammednazaar, Jiaqi Yao, Matthew R Nicelis, Yein Christina Park, Zhongtian Shen, Michael D Bridges, Ruiqiong Guo, Nicole Swope, May Seunghyo Rhee, Miyeon Kim, Kelly Hyojin Kim, Wayne L Hubbell, Karen G Fleming, Linda Columbus, Seung-gu Kang, and Heedeok Hong.
bioRxiv posted 24 December 2024.
doi:10.1101/2023.05.30.542905.
Study exploring how diverse amphiphilic environments stabilize membrane proteins => hydrophobic thickness and amphiphile packing strength are key factors.
Lipids enhance stability by aiding residue burial within the protein and reinforcing structural cooperativity.
Dual role of lipids in modulating membrane protein stability and their responsiveness to external stimuli.
Microarray-Based Methodology for Lipid Profiling Enzymatic Activity And Binding Assays in Printed Lipid Raft Membranes from Astrocytes and Neurons.
Sánchez-Sánchez L Fernández R Astigarraga E Barreda-Gómez G Ganfornina MD.
Anal Chem. 2024 Dec 24.
doi: 10.1021/acs.analchem.4c02421. Online ahead of print.
PMID: 39718364.
Development of raft membrane microarrays (RMMAs) allows for the study of lipid and protein dynamics in these subdomains.
Here: by applying RMMA to astrocytes and neurons under various conditions, the study evaluates lipid profiles and protein activities => insights into neuropathology-related stress conditions.
Approaching Ideal Selectivity with Bioinspired and Biomimetic Membranes.
Oh H Samineni L Vogler RJ Yao C Behera H Dhiman R Horner A Kumar M.
ACS Nano. 2024 Dec 24.
doi: 10.1021/acsnano.4c09699. Online ahead of print.
PMID: 39718215.
Review exploring the mechanisms behind transport in biological membranes, highlights the advancements in bioinspired and biomimetic membranes fabrication.
Lipid bilayers determine the allostery but not intrinsic affinity of cAMP binding to pacemaker channels.
Vinay Idikuda, Susovan Roy Chowdhury, Yongchang Chang, Qian Ren, Huan Bao, Randall H. Goldsmith, Baron Chanda.
bioRxiv 2024.12.23.630133;
doi: https://doi.org/10.1101/2024.12.23.630133.
In the human heart, cAMP regulates pacemaker cell automaticity by binding to hyperpolarization and cyclic nucleotide-gated (HCN) channels.
Here: reconstitution of purified HCN channels in ND => lipid membranes promote cooperative cAMP binding between subunits, enhancing ion channel gating sensitivity without affecting the intrinsic binding affinity.
+ cryo-EM structures => critical role of lipid membranes in amplifying inter-subunit interactions.
Biochemical characterization and mutational analysis of lysophosphatidic acid acyltransferases of Escherichia coli highlighting their involvement in the generation of membrane phospholipid diversity.
Suwanawat N Ogawa T Toyotake Y Kawamoto J Kurihara T.
J Biochem. 2024 Dec 27:mvae093.
doi: 10.1093/jb/mvae093. Online ahead of print.
PMID: 39727331.
Lysophosphatidic acid acyltransferase (LPAAT) enzymes catalyze the conversion of lysophosphatidic acid to phosphatidic acid.
Here: mutational analysis => key residue involved in substrate selectivity.
Lipids modulate open probability of RyR1 under cryo-EM conditions
Chenyao Li and Rouslan G. Efremov
bioRxiv posted 21 December 2024
doi:10.1101/2024.12.20.629683
RyRs = ion channels that regulate calcium release from intracellular stores (RyR1 is essential for muscle contraction).
Here: cryo-EM studies of RyR1 => increasing lipid concentration can significantly increase its open probability but reconstitution into lipid nanodiscs keeps it closed.
=> Role of lipids in modulating RyR1 gating and suggests optimal lipid-mimetic conditions for structural investigations of RyR1 gating mechanisms.
Molecules
Tunable Terpolymer Series for the Systematic Investigation of Membrane Proteins.
Kuyler GC Barnard E Sridhar P Murray RJ Pollock NL Wheatley M Dafforn TR Klumperman B.
Biomacromolecules. 2024 Dec 26.
doi: 10.1021/acs.biomac.4c01219. Online ahead of print.
PMID: 39725644.
Introduction of a series of novel poly(styrene-co-maleic acid-co-(N-benzyl)maleimide) (BzAM) terpolymers.
These terpolymers exhibit tunable amphiphilicity => effective membrane solubilization while preserving the structural and functional integrity of MPs, such as Sav1866.
=> direct correlation between polymer hydrophobicity and solubilization efficiency.
Methods
Light-Controlled Secretion and Injection of Proteins into Eukaryotic Cells by Optogenetic Control of the Bacterial Type III Secretion System.
Lindner F, Grossmann S, Diepold A.
Methods Mol Biol. 2025;2840:115-131.
doi: 10.1007/978-1-0716-4047-0_9.
PMID: 39724348.
Application of a light-controlled T3SS, based on the targeted sequestration of an essential dynamic T3SS component with the help of optogenetic interaction switches.
=> Enables to control the secretion or injection into eukaryotic cells for a wide range of protein cargos with high temporal and spatial precision.
An improvised one-step OptiPrep cushion ultracentrifugation method for outer membrane vesicles isolation of Klebsiella pneumoniae.
Li P Lu M Peng T Wu Y Zhu L Liu Y Zhang W Xiang T.
BMC Microbiol. 2024 Dec 2824(1):548.
doi: 10.1186/s12866-024-03649-y.
PMID: 39732632.
Dual differential gradient centrifugation (DDGC) method for extracting OMVs from K. pneumoniae, combining traditional differential centrifugation with one-step ultracentrifugation.
DDGC extracted OMVs with improved morphology, clearer backgrounds, and more uniform particle size distribution, along with higher LPS and OM protein content.
End-to-end neural ab initio reconstruction of challenging cryo-EM and cryo-ET datasets.
Axel Levy, Rishwanth Raghu, J. Ryan Feathers, Michal Grzadkowski, Frederic Poitevin, Francesca Vallese, Oliver B Clarke, Gordon Wetzstein, and Ellen D Zhong.
bioRxiv posted 24 December 2024
doi:10.1101/2024.05.30.596729.
DRGN-AI = novel method to process challenging cryo-EM and cryo-ET datasets => enables description of new conformational states, reconstruction of unresolved motions, and ab initio reconstructions of biomolecular complexes directly from in situ data.
Useful experimental aspects of small-wedge synchrotron crystallography for accurate structure analysis of protein molecules.
Hirata K.
Acta Crystallogr D Struct Biol. 2025 Jan 1.
doi: 10.1107/S2059798324011987. Online ahead of print.
PMID: 39718396.
Recent advances in synchrotron X-ray technology and photon-counting detectors have revolutionized protein micro-crystallography, enabling automated, high-efficiency data collection.
Here: use of small-wedge synchrotron crystallography (SWSX) to improve data collection efficiency for protein structures.
Integration of ML for data classification and analysis = critical in enhancing data quality.
DeepETPicker: Fast and accurate 3D particle picking for cryo-electron tomography using weakly supervised deep learning.
Liu G, Niu T, Qiu M, Zhu Y, Sun F, Yang G.
Nat Commun. 2024 Mar 7;15(1):2090.
doi: 10.1038/s41467-024-46041-0.
PMID: 38453943.
DeepETPicker = deep learning model to automate the particle-picking process from cryo-ET.
Available as an open-source tool with a user-friendly interface for cryo-electron tomography applications.
Demonstrating Soft X-Ray Tomography in the lab for correlative cryogenic biological imaging using X-rays and light microscopy.
Stephen O’Connor David Rogers Maryna Kobylynska James Geraets Katja Thaysen Jacob Marcus Egebjerg Madeleen C. Brink Louisa Herbsleb Michaela Salakova Leon Fuchs Frauke Alves Claus Feldmann Axel Ekman Paul Sheridan William Fyans Tony McEnroe Fergal O’Reilly Kenneth Fahy Roland A. Fleck Daniel Wüstner Jeremy C. Simpson Andreas Walter and Sergey Kapishnikov.
bioRxiv posted 23 December 2024.
doi:10.1101/2024.12.23.629889.
Soft X-ray tomography provides high-resolution 3D imaging of cryopreserved biological samples without the need for staining or sectioning, with resolutions down to 54 nm.
Description of the SXT-100 microscope that integrates fluorescence microscopy for correlative imaging: rapid and non-destructive imaging capabilities.
Microbio
How microbial growth adapts to temperature shifts.
Nat Microbiol. 2024 Dec 23.
doi: 10.1038/s41564-024-01847-y. Epub ahead of print.
PMID: 39715920.
Study showing that the dynamics of metabolomic rearrangement => growth response of bacteria and fungi to rapid changes in temperature.
Single-cell microscopy revealed a mechanism for transient memory of previous temperatures and indicated that these responses are generally conserved.
Indole phytochemical camalexin as a promising scaffold for AcrB efflux pump inhibitors against Escherichia coli.
Irianti MI Malloci G Ruggerone P Lodinsky EV Vincken JP Pos KM Araya-Cloutier C.
Biomed Pharmacother. 2024 Dec 27182:117779.
doi: 10.1016/j.biopha.2024.117779. Online ahead of print.
PMID: 39731937.
Characterisation of camalexin and brassinin as potential inhibitors of E. coli AcrB.
Camalexin: increase EthB accumulation / significant reduction of MIC of antibiotics.
Docking simulations => camalexin binds more stably to AcrB than brassinin.
Miscellaneous
A mathematical model for the determination of total area under glucose tolerance and other metabolic curves.
Tai MM.
Diabetes Care. 1994 Feb;17(2):152-4.
doi: 10.2337/diacare.17.2.152.
PMID: 8137688.
”When I have imposter syndrome, I think about this 1994 paper when a nutrition researcher reinvent integration, and name it after herself”. @sylvaingigan.bsky.social
Oldest cooked leftovers ever found suggest Neanderthals were foodies
A couple of years ago researchers discovered the oldest cooked meal ever found: a tasty-sounding seed flatbread that might have been cooked by Neanderthals 70000 years ago.
Here: modern version of this recipe.
Ingredients: Two parts grass seeds (authors recommend wheat berries or pot barley One part lentils — try brown or Puy lentils)
Soak everything overnight and then drain.
Grind in a pestle and mortar or use a stick blender if you must.
Keep going until you have a mush with most components “in the 1-2 millimetre or smaller range” — add a little water as you go if needed.
Add more water until you have a thick paste.
Scoop some mixture onto a flat griddle or frying pan.
Cook gently browning on each side. “Better for 15–20 minutes on a low heat rather than getting things really smoking!”.
Fast-forward 30000 years and there is evidence that food was more diverse including fruit from the terebinth (related to the pistachio) a wild precursor of the fava bean and mustard seeds as well as wild grasses and wild lentils. And there is separate evidence that Neanderthals ate almonds.
Add modern versions of these to your mix and you’ll find the taste “significantly more interesting”. Combining it with grilled goat or fish would also be “quite legitimate” he adds.