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283 items found (0 items not approved), displaying 1 to 10.[First/Prev] 1, 2, 3, 4, 5, 6, 7, 8 [Next/Last]

Instruments / Technical Area	Publication Details	Published
Krios III-Titan Krios III at Diamond	Structures of the human adult muscle-type nicotinic receptor in resting and desensitized states Anna Li , Ashley C. W. Pike , Richard Webster , Susan Maxwell , Wei-Wei Liu , Gamma Chi , Jacqueline Palace , David Beeson , David B. Sauer , Yin Yao Dong Cell Reports 44 DOI: 10.1016/j.celrep.2025.115581 Diamond Proposal Number(s): [28713] Open Access Show Abstract ▼ Abstract: Muscle-type nicotinic acetylcholine receptor (AChR) is the key signaling molecule in neuromuscular junctions. Here, we present the structures of full-length human adult receptors in complex with Fab35 in α-bungarotoxin (αBuTx)-bound resting states and ACh-bound desensitized states. In addition to identifying the conformational changes during recovery from desensitization, we also used electrophysiology to probe the effects of eight previously unstudied AChR genetic variants found in patients with congenital myasthenic syndrome (CMS), revealing they cause either slow- or fast-channel CMS characterized by prolonged or abbreviated ion channel bursts. The combined kinetic and structural data offer a better understanding of both the AChR state transition and the pathogenic mechanisms of disease variants.	May 2025
	Tethering ferredoxin-NADP+ reductase to photosystem I promotes photosynthetic cyclic electron transfer Thomas Z. Emrich-Mills , Matthew S. Proctor , Gustaf E. Degen , Philip J. Jackson , Katherine H. Richardson , Frederick R. Hawkings , Felix Buchert , Andrew Hitchcock , C. Neil Hunter , Luke C. M. Mackinder , Michael Hippler , Matthew P. Johnson The Plant Cell DOI: 10.1093/plcell/koaf042 Open Access Show Abstract ▼ Abstract: Fixing CO2 via photosynthesis requires ATP and NADPH, which can be generated through linear electron transfer (LET). However, depending on the environmental conditions, additional ATP may be required to fix CO2, which can be generated by cyclic electron transfer (CET). How the balance between LET and CET is determined remains largely unknown. Ferredoxin-NADP+ reductase (FNR) may act as the switch between LET and CET, channelling photosynthetic electrons to LET when it is bound to photosystem I (PSI) or to CET when it is bound to cytochrome b6f. The essential role of FNR in LET precludes the use of a direct gene knock-out to test this hypothesis. Nevertheless, we circumvented this problem using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated gene editing in Chlamydomonas reinhardtii. Through this approach, we created a chimeric form of FNR tethered to PSI via PSAF. Chimeric FNR mutants exhibited impaired photosynthetic growth and LET along with enhanced PSI acceptor side limitation relative to the wild type due to slower NADPH reduction. However, the chimeric FNR mutants also showed enhanced ΔpH production and NPQ resulting from increased CET. Overall, our results suggest that rather than promoting LET, tethering FNR to PSI promotes CET at the expense of LET and CO2 fixation.	Mar 2025
B21-High Throughput SAXS	Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends Saishree S. Iyer , Fangrui Chen , Funso E. Ogunmolu , Shoeib Moradi , Vladimir A. Volkov , Emma J. Van Grinsven , Chris Van Hoorn , Jingchao Wu , Nemo Andrea , Shasha Hua , Kai Jiang , Ioannis Vakonakis , Mia Potočnjak , Franz Herzog , Benoît Gigant , Nikita Gudimchuk , Kelly E. Stecker , Marileen Dogterom , Michel O. Steinmetz , Anna Akhmanova Journal Of Cell Biology 224 DOI: 10.1083/jcb.202406061 Diamond Proposal Number(s): [21035] Open Access Show Abstract ▼ Abstract: Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4. We found that whereas CEP97 does not bind to microtubules directly, CP110 autonomously binds microtubule plus ends, blocks their growth, and inhibits depolymerization. Cryo-electron tomography revealed that CP110 associates with the luminal side of microtubule plus ends and suppresses protofilament flaring. CP110 directly interacts with CPAP, which acts as a microtubule polymerase that overcomes CP110-induced growth inhibition. Together, the two proteins impose extremely slow processive microtubule growth. Disruption of CP110–CPAP interaction in cells inhibits centriole elongation and increases incidence of centriole defects. Our findings reveal how two centriolar cap proteins with opposing activities regulate microtubule plus-end elongation and explain their antagonistic relationship during centriole formation.	Mar 2025
I19-Small Molecule Single Crystal Diffraction	Encapsulation of hydrophobic pollutants within a large water-soluble [Fe4L6]4− cage Jack D. Wright , George F. S. Whitehead , Edward O. Pyzer-Knapp , Imogen A. Riddell Cell Reports Physical Science 9 DOI: 10.1016/j.xcrp.2025.102404 Diamond Proposal Number(s): [31541] Open Access Show Abstract ▼ Abstract: Hydrophobic molecules lost in water systems can have significant impacts on local ecology. Notably, the discharge of unmetabolized medications, specifically hormones, and hygiene products into effluent wastewater is a pressing environmental challenge. While selective capture of these molecules has been demonstrated by metal-organic cages (MOCs), these studies typically employ an organic solvent system that does not reflect aqueous environmental conditions. In this study, we report a rare, water-soluble, tetrahedral MOC bearing hydrosolvating sulfonate moieties alongside an aromatic naphthyl spacer. The MOC encloses a large (657 Å3) cavity that can bind a range of polycyclic structures in aqueous media. Isothermal titration calorimetry measurements support guest binding being an enthalpically driven hydrophobic binding process. The synthetic strategy employed to prepare the MOC is extensible and thus serves as a promising route to a range of large, water-soluble MOCs containing hydrophobic binding cavities with exciting prospects.	Jan 2025
I03-Macromolecular Crystallography I04-Macromolecular Crystallography	Biochemical and structural characterization of enzymes in the 4-hydroxybenzoate catabolic pathway of lignin-degrading white-rot fungi Eugene Kuatsjah , Alexa Schwartz , Michael Zahn , Konstantinos Tornesakis , Zoe A. Kellermyer , Morgan A. Ingraham , Sean P. Woodworth , Kelsey J. Ramirez , Paul A. Cox , Andrew R. Pickford , Davinia Salvachúa Cell Reports 43 DOI: 10.1016/j.celrep.2024.115002 Diamond Proposal Number(s): [23269] Open Access Show Abstract ▼ Abstract: White-rot fungi (WRF) are the most efficient lignin-degrading organisms in nature. However, their capacity to use lignin-related aromatic compounds, such as 4-hydroxybenzoate, as carbon sources has only been described recently. Previously, the hydroxyquinol pathway was proposed for the bioconversion of these compounds in fungi, but gene- and structure-function relationships of the full enzymatic pathway remain uncharacterized in any single fungal species. Here, we characterize seven enzymes from two WRF, Trametes versicolor and Gelatoporia subvermispora, which constitute a four-enzyme cascade from 4-hydroxybenzoate to β-ketoadipate via the hydroxyquinol pathway. Furthermore, we solve the crystal structure of four of these enzymes and identify mechanistic differences with the closest bacterial and fungal structural homologs. Overall, this research expands our understanding of aromatic catabolism by WRF and establishes an alternative strategy for the conversion of lignin-related compounds to the valuable molecule β-ketoadipate, contributing to the development of biological processes for lignin valorization.	Dec 2024
I11-High Resolution Powder Diffraction	High-entropy sulfide argyrodite electrolytes for all-solid-state lithium-sulfur batteries Hua Guo , Junhao Li , Matthew Burton , John Cattermull , Yi Liang , Yvonne Chart , Gregory J. Rees , Jack Aspinall , Mauro Pasta Cell Reports Physical Science 120 DOI: 10.1016/j.xcrp.2024.102228 Diamond Proposal Number(s): [25166] Open Access Show Abstract ▼ Abstract: Solid-state electrolytes (SEs) hold the potential to overcome challenges that hinder the commercialization of lithium-sulfur batteries. However, their limited ionic conductivity makes lithium (Li) ion transport a critical bottleneck in accessing the superior capacity of sulfur. In this study, we investigate high-entropy Cl,Br-co-doped sulfide argyrodites as SEs in Li-sulfur (S) all-solid-state batteries (ASSBs). exhibits an ionic conductivity of 6.9 mS at room temperature with an activation energy of 0.28 eV, thanks to its high configurational entropy. The electrolyte with suitable cathodic stability and high ionic conductivity allows S composite cathodes to deliver an areal capacity over 6 mAh when cycled with Li-In anodes. The reduced porosity of the SE separator and the formation of a passivating interphase with metallic Li enable Li-S ASSBs to cycle without short circuits, achieving an S utilization of over 75% at 0.1 C.	Oct 2024
Krios III-Titan Krios III at Diamond Krios IV-Titan Krios IV at Diamond	Adaptive multi-epitope targeting and avidity-enhanced nanobody platform for ultrapotent, durable antiviral therapy Yufei Xiang , Jialu Xu , Briana L. Mcgovern , Anna Ranzenigo , Wei Huang , Zhe Sang , Juan Shen , Randy Diaz-Tapia , Ngoc Dung Pham , Abraham J. P. Teunissen , M. Luis Rodriguez , Jared Benjamin , Derek J. Taylor , Mandy M. T. Van Leent , Kris M. White , Adolfo García-Sastre , Peijun Zhang , Yi Shi Cell 19 DOI: 10.1016/j.cell.2024.09.043 Show Abstract ▼ Abstract: Pathogens constantly evolve and can develop mutations that evade host immunity and treatment. Addressing these escape mechanisms requires targeting evolutionarily conserved vulnerabilities, as mutations in these regions often impose fitness costs. We introduce adaptive multi-epitope targeting with enhanced avidity (AMETA), a modular and multivalent nanobody platform that conjugates potent bispecific nanobodies to a human immunoglobulin M (IgM) scaffold. AMETA can display 20+ nanobodies, enabling superior avidity binding to multiple conserved and neutralizing epitopes. By leveraging multi-epitope SARS-CoV-2 nanobodies and structure-guided design, AMETA constructs exponentially enhance antiviral potency, surpassing monomeric nanobodies by over a million-fold. These constructs demonstrate ultrapotent, broad, and durable efficacy against pathogenic sarbecoviruses, including Omicron sublineages, with robust preclinical results. Structural analysis through cryoelectron microscopy and modeling has uncovered multiple antiviral mechanisms within a single construct. At picomolar to nanomolar concentrations, AMETA efficiently induces inter-spike and inter-virus cross-linking, promoting spike post-fusion and striking viral disarmament. AMETA’s modularity enables rapid, cost-effective production and adaptation to evolving pathogens.	Oct 2024
	CryoVesNet: A dedicated framework for synaptic vesicle segmentation in cryo-electron tomograms Amin Khosrozadeh , Raphaela Seeger , Guillaume Witz , Julika Radecke , Jakob B. Sørensen , Benoît Zuber Journal Of Cell Biology 224 DOI: 10.1083/jcb.202402169 Show Abstract ▼ Abstract: Cryo-electron tomography (cryo-ET) has the potential to reveal cell structure down to atomic resolution. Nevertheless, cellular cryo-ET data is highly complex, requiring image segmentation for visualization and quantification of subcellular structures. Due to noise and anisotropic resolution in cryo-ET data, automatic segmentation based on classical computer vision approaches usually does not perform satisfactorily. Communication between neurons relies on neurotransmitter-filled synaptic vesicle (SV) exocytosis. Cryo-ET study of the spatial organization of SVs and their interconnections allows a better understanding of the mechanisms of exocytosis regulation. Accurate SV segmentation is a prerequisite to obtaining a faithful connectivity representation. Hundreds of SVs are present in a synapse, and their manual segmentation is a bottleneck. We addressed this by designing a workflow consisting of a convolutional network followed by post-processing steps. Alongside, we provide an interactive tool for accurately segmenting spherical vesicles. Our pipeline can in principle segment spherical vesicles in any cell type as well as extracellular and in vitro spherical vesicles.	Oct 2024
Krios I-Titan Krios I at Diamond	Stabilization of the hexasome intermediate during histone exchange by yeast SWR1 complex Adam S. B. Jalal , Paul Girvan , Eugene Y. D. Chua , Lexin Liu , Shijie Wang , Elizabeth A. Mccormack , Michael T. Skehan , Carol L. Knight , David S. Rueda , Dale B. Wigley Molecular Cell 12 DOI: 10.1016/j.molcel.2024.08.015 Diamond Proposal Number(s): [36390] Open Access Show Abstract ▼ Abstract: The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine the structure of an enzyme-bound hexasome intermediate in the reaction pathway of histone exchange, in which an H2A/H2B dimer has been extracted from a nucleosome prior to the insertion of a dimer comprising Htz1/H2B. The structure reveals a key role for the Swc5 subunit in stabilizing the unwrapping of DNA from the histone core of the hexasome. By engineering a crosslink between an Htz1/H2B dimer and its chaperone protein Chz1, we show that this blocks histone exchange by SWR1 but allows the incoming chaperone-dimer complex to insert into the hexasome. We use this reagent to trap an SWR1/hexasome complex with an incoming Htz1/H2B dimer that shows how the reaction progresses to the next step. Taken together the structures reveal insights into the mechanism of histone exchange by SWR1 complex.	Sep 2024
Krios III-Titan Krios III at Diamond	CDK5RAP2 activates microtubule nucleator γTuRC by facilitating template formation and actin release Marina Serna , Fabian Zimmermann , Chithran Vineethakumari , Nayim Gonzalez-Rodriguez , Oscar Llorca , Jens Lüders Developmental Cell 28 DOI: 10.1016/j.devcel.2024.09.001 Diamond Proposal Number(s): [26876] Show Abstract ▼ Abstract: To organize microtubules, cells tightly control the activity of the microtubule nucleator γ-tubulin ring complex (γTuRC). The open ring-shaped γTuRC was proposed to nucleate microtubules by a template mechanism. However, its splayed structure does not match microtubule symmetry, leaving it unclear how γTuRC becomes an efficient nucleator. Here, we identify the mechanism of γTuRC activation by CDK5RAP2 centrosomin motif 1 (CM1). Using cryoelectron microscopy (cryo-EM), we find that activation involves binding of multiple CM1 dimers to five distinct sites around the outside of the γTuRC cone, which crucially depends on regulatory modules formed by MZT2 and the N-terminal extensions of GCP2 subunits. CM1 binding promotes lateral interactions between GCP subunits to facilitate microtubule-like conformations and release of luminal actin that is integral to non-activated γTuRC. We propose a model where generation of γTuRC with an expanded conformational range, rather than perfect symmetry, is sufficient to boost nucleation activity.	Sep 2024

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