I06-Nanoscience
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Hariom
Jani
,
Jheng-cyuan
Lin
,
Jiahao
Chen
,
Jack
Harrison
,
Francesco
Maccherozzi
,
Jonathon
Schad
,
Saurav
Prakash
,
Chang-beom
Eom
,
A.
Ariando
,
Thirumalai
Venkatesan
,
Paolo G.
Radaelli
Diamond Proposal Number(s):
[23857, 20317]
Abstract: In the quest for post-CMOS (complementary metal–oxide–semiconductor) technologies, driven by the need for improved efficiency and performance, topologically protected ferromagnetic ‘whirls’ such as skyrmions and their anti-particles have shown great promise as solitonic information carriers in racetrack memory-in-logic or neuromorphic devices. However, the presence of dipolar fields in ferromagnets, which restricts the formation of ultrasmall topological textures, and the deleterious skyrmion Hall effect, when skyrmions are driven by spin torques have thus far inhibited their practical implementation. Antiferromagnetic analogues, which are predicted to demonstrate relativistic dynamics, fast deflection-free motion and size scaling, have recently become the subject of intense focus, but they have yet to be experimentally demonstrated in natural antiferromagnetic systems. Here we realize a family of topological antiferromagnetic spin textures in α-Fe2O3—an Earth-abundant oxide insulator—capped with a platinum overlayer. By exploiting a first-order analogue of the Kibble–Zurek mechanism2, we stabilize exotic merons and antimerons (half-skyrmions)8 and their pairs (bimerons), which can be erased by magnetic fields and regenerated by temperature cycling. These structures have characteristic sizes of the order of 100 nanometres and can be chemically controlled via precise tuning of the exchange and anisotropy, with pathways through which further scaling may be achieved. Driven by current-based spin torques from the heavy-metal overlayer, some of these antiferromagnetic textures could emerge as prime candidates for low-energy antiferromagnetic spintronics at room temperature.
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Feb 2021
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Iain W.
Mcnae
,
James
Kinkead
,
Divya
Malik
,
Li-hsuan
Yen
,
Martin K.
Walker
,
Chris
Swain
,
Scott P.
Webster
,
Nick
Gray
,
Peter M.
Fernandes
,
Elmarie
Myburgh
,
Elizabeth
Blackburn
,
Ryan
Ritchie
,
Carol
Austin
,
Martin A.
Wear
,
Adrian J.
Highton
,
Andrew J.
Keats
,
Antonio
Vong
,
Jacqueline
Dornan
,
Jeremy C.
Mottram
,
Paul A. M.
Michels
,
Simon
Pettit
,
Malcolm D.
Walkinshaw
Diamond Proposal Number(s):
[9487, 13550]
Open Access
Abstract: The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
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Feb 2021
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Shanshan
Zhou
,
Hussain
Bhukya
,
Nicolas
Malet
,
Peter J.
Harrison
,
Dean
Rea
,
Matthew J.
Belousoff
,
Hariprasad
Venugopal
,
Paulina K.
Sydor
,
Kathryn M.
Styles
,
Lijiang
Song
,
Max J.
Cryle
,
Lona M.
Alkhalaf
,
Vilmos
Fulop
,
Gregory L.
Challis
,
Christophe
Corre
Diamond Proposal Number(s):
[8359, 8388]
Abstract: Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR–AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR–operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.
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Feb 2021
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[15916, 21426]
Open Access
Abstract: Attachment of ubiquitin (Ub) to proteins is one of the most abundant and versatile of all posttranslational modifications and affects outcomes in essentially all physiological processes. RING E3 ligases target E2 Ub-conjugating enzymes to the substrate, resulting in its ubiquitination. However, the mechanism by which a ubiquitin chain is formed on the substrate remains elusive. Here we demonstrate how substrate binding can induce a specific RING topology that enables self-ubiquitination. By analyzing a catalytically trapped structure showing the initiation of TRIM21 RING-anchored ubiquitin chain elongation, and in combination with a kinetic study, we illuminate the chemical mechanism of ubiquitin conjugation. Moreover, biochemical and cellular experiments show that the topology found in the structure can be induced by substrate binding. Our results provide insights into ubiquitin chain formation on a structural, biochemical and cellular level with broad implications for targeted protein degradation.
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Feb 2021
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[14692]
Open Access
Abstract: Bacterial hybrid malic enzymes (MaeB grouping, multidomain) catalyse the transformation of malate to pyruvate, and are a major contributor to cellular reducing power and carbon flux. Distinct from other malic enzyme subtypes, the hybrid enzymes are regulated by acetyl-CoA, a molecular indicator of the metabolic state of the cell. Here we solve the structure of a MaeB protein, which reveals hybrid enzymes use the appended phosphotransacetylase (PTA) domain to form a hexameric sensor that communicates acetyl-CoA occupancy to the malic enzyme active site, 60 Å away. We demonstrate that allostery is governed by a large-scale rearrangement that rotates the catalytic subunits 70° between the two states, identifying MaeB as a new model enzyme for the study of ligand-induced conformational change. Our work provides the mechanistic basis for metabolic control of hybrid malic enzymes, and identifies inhibition-insensitive variants that may find utility in synthetic biology.
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Feb 2021
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Krios IV-Titan Krios IV at Diamond
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Max
Renner
,
Wanwisa
Dejnirattisai
,
Loic
Carrique
,
Itziar
Serna Martin
,
Dimple
Karia
,
Serban L.
Ilca
,
Shu F.
Ho
,
Abhay
Kotecha
,
Jeremy R.
Keown
,
Juthathip
Mongkolsapaya
,
Gavin R.
Screaton
,
Jonathan M.
Grimes
Diamond Proposal Number(s):
[20223]
Open Access
Abstract: Flaviviruses such as Dengue (DENV) or Zika virus (ZIKV) assemble into an immature form within the endoplasmatic reticulum (ER), and are then processed by furin protease in the trans-Golgi. To better grasp maturation, we carry out cryo-EM reconstructions of immature Spondweni virus (SPOV), a human flavivirus of the same serogroup as ZIKV. By employing asymmetric localised reconstruction we push the resolution to 3.8 Å, enabling us to refine an atomic model which includes the crucial furin protease recognition site and a conserved Histidine pH-sensor. For direct comparison, we also solve structures of the mature forms of SPONV and DENV to 2.6 Å and 3.1 Å, respectively. We identify an ordered lipid that is present in only the mature forms of ZIKV, SPOV, and DENV and can bind as a consequence of rearranging amphipathic stem-helices of E during maturation. We propose a structural role for the pocket and suggest it stabilizes mature E.
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Feb 2021
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I11-High Resolution Powder Diffraction
I20-EDE-Energy Dispersive EXAFS (EDE)
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Longfei
Lin
,
Mengtian
Fan
,
Alena M.
Sheveleva
,
Xue
Han
,
Zhimou
Tang
,
Joseph H.
Carter
,
Ivan
Da Silva
,
Christopher
Parlett
,
Floriana
Tuna
,
Eric J. L.
Mcinnes
,
German
Sastre
,
Svemir
Rudic
,
Hamish
Cavaye
,
Stewart F.
Parker
,
Yongqiang
Cheng
,
Luke L.
Daemen
,
Anibal J.
Ramirez-cuesta
,
Martin P.
Attfield
,
Yueming
Liu
,
Chiu C.
Tang
,
Buxing
Han
,
Sihai
Yang
Diamond Proposal Number(s):
[2359]
Open Access
Abstract: Optimising the balance between propene selectivity, propene/ethene ratio and catalytic stability and unravelling the explicit mechanism on formation of the first carbon–carbon bond are challenging goals of great importance in state-of-the-art methanol-to-olefin (MTO) research. We report a strategy to finely control the nature of active sites within the pores of commercial MFI-zeolites by incorporating tantalum(V) and aluminium(III) centres into the framework. The resultant TaAlS-1 zeolite exhibits simultaneously remarkable propene selectivity (51%), propene/ethene ratio (8.3) and catalytic stability (>50 h) at full methanol conversion. In situ synchrotron X-ray powder diffraction, X-ray absorption spectroscopy and inelastic neutron scattering coupled with DFT calculations reveal that the first carbon–carbon bond is formed between an activated methanol molecule and a trimethyloxonium intermediate. The unprecedented cooperativity between tantalum(V) and Brønsted acid sites creates an optimal microenvironment for efficient conversion of methanol and thus greatly promotes the application of zeolites in the sustainable manufacturing of light olefins.
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Feb 2021
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
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Declan A.
Gray
,
Joshua B. R.
White
,
Abraham O.
Oluwole
,
Parthasarathi
Rath
,
Amy J.
Glenwright
,
Adam
Mazur
,
Michael
Zahn
,
Arnaud
Basle
,
Carl
Morland
,
Sasha L.
Evans
,
Alan
Cartmell
,
Carol V.
Robinson
,
Sebastian
Hiller
,
Neil A.
Ranson
,
David N.
Bolam
,
Bert
Van Den Berg
Diamond Proposal Number(s):
[13587, 18598]
Open Access
Abstract: In Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ~2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.
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Jan 2021
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I05-ARPES
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Wujun
Shi
,
Benjamin J.
Wieder
,
Holger L.
Meyerheim
,
Yan
Sun
,
Yang
Zhang
,
Yiwei
Li
,
Lei
Shen
,
Yanpeng
Qi
,
Lexian
Yang
,
Jagannath
Jena
,
Peter
Werner
,
Klaus
Koepernik
,
Stuart
Parkin
,
Yulin
Chen
,
Claudia
Felser
,
B. Andrei
Bernevig
,
Zhijun
Wang
Abstract: Topological physics and strong electron–electron correlations in quantum materials are typically studied independently. However, there have been rapid recent developments in quantum materials in which topological phase transitions emerge when the single-particle band structure is modified by strong interactions. Here we demonstrate that the room-temperature phase of (TaSe4)2I is a Weyl semimetal with 24 pairs of Weyl nodes. Owing to its quasi-one-dimensional structure, (TaSe4)2I also hosts an established charge-density wave instability just below room temperature. We show that the charge-density wave in (TaSe4)2I couples the bulk Weyl points and opens a bandgap. The correlation-driven topological phase transition in (TaSe4)2I provides a route towards observing condensed-matter realizations of axion electrodynamics in the gapped regime, topological chiral response effects in the semimetallic phase, and represents an avenue for exploring the interplay of correlations and topology in a solid-state material.
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Jan 2021
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I15-1-X-ray Pair Distribution Function (XPDF)
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Xiao
Hua
,
Alexander S.
Eggeman
,
Elizabeth
Castillo-martinez
,
Rosa
Robert
,
Harry S.
Geddes
,
Ziheng
Lu
,
Chris J.
Pickard
,
Wei
Meng
,
Kamila M.
Wiaderek
,
Nathalie
Pereira
,
Glenn G.
Amatucci
,
Paul A.
Midgley
,
Karena W.
Chapman
,
Ullrich
Steiner
,
Andrew L.
Goodwin
,
Clare
Grey
Diamond Proposal Number(s):
[17315]
Abstract: Metal fluorides, promising lithium-ion battery cathode materials, have been classified as conversion materials due to the reconstructive phase transitions widely presumed to occur upon lithiation. We challenge this view by studying FeF3 using X-ray total scattering and electron diffraction techniques that measure structure over multiple length scales coupled with density functional theory calculations, and by revisiting prior experimental studies of FeF2 and CuF2. Metal fluoride lithiation is instead dominated by diffusion-controlled displacement mechanisms, and a clear topological relationship between the metal fluoride F− sublattices and that of LiF is established. Initial lithiation of FeF3 forms FeF2 on the particle’s surface, along with a cation-ordered and stacking-disordered phase, A-LixFeyF3, which is structurally related to α-/β-LiMn2+Fe3+F6 and which topotactically transforms to B- and then C-LixFeyF3, before forming LiF and Fe. Lithiation of FeF2 and CuF2 results in a buffer phase between FeF2/CuF2 and LiF. The resulting principles will aid future developments of a wider range of isomorphic metal fluorides.
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Jan 2021
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