I04-Macromolecular Crystallography
|
Diamond Proposal Number(s):
[14843]
Open Access
Abstract: Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. As non-enveloped, double-stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus type 26 (HAdV-D26) is both a cause of EKC and other diseases and a promising vaccine vector. HAdV-D26–derived vaccines are under investigation as protective platforms against HIV, Zika, and respiratory syncytial virus infections and are in phase 3 clinical trials for Ebola. We recently demonstrated that HAdV-D26 does not use CD46 or Desmoglein-2 as entry receptors, while the putative interaction with coxsackie and adenovirus receptor is low affinity and unlikely to represent the primary cell receptor. Here, we establish sialic acid as a primary entry receptor used by HAdV-D26. We demonstrate that removal of cell surface sialic acid inhibits HAdV-D26 infection, and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid.
|
Sep 2019
|
|
Krios II-Titan Krios II at Diamond
|
Diamond Proposal Number(s):
[19832]
Open Access
Abstract: Quinol-dependent nitric oxide reductases (qNORs) are membrane-integrated, iron-containing enzymes of the denitrification pathway, which catalyze the reduction of nitric oxide (NO) to the major ozone destroying gas nitrous oxide (N2O). Cryo–electron microscopy structures of active qNOR from Alcaligenes xylosoxidans and an activity-enhancing mutant have been determined to be at local resolutions of 3.7 and 3.2 Å, respectively. They unexpectedly reveal a dimeric conformation (also confirmed for qNOR from Neisseria meningitidis) and define the active-site configuration, with a clear water channel from the cytoplasm. Structure-based mutagenesis has identified key residues involved in proton transport and substrate delivery to the active site of qNORs. The proton supply direction differs from cytochrome c–dependent NOR (cNOR), where water molecules from the cytoplasm serve as a proton source similar to those from cytochrome c oxidase.
|
Aug 2019
|
|
I04-1-Macromolecular Crystallography (fixed wavelength)
|
Miranda P.
Collier
,
T. Reid
Alderson
,
Carin P.
De Villiers
,
Daisy
Nicholls
,
Heidi Y.
Gastall
,
Timothy
Allison
,
Matteo T.
Degiacomi
,
He
Jiang
,
Georg
Mlynek
,
Dieter O.
Fürst
,
Peter F. M.
Van Der Ven
,
Kristina
Djinovic-carugo
,
Andrew J.
Baldwin
,
Hugh
Watkins
,
Katja
Gehmlich
,
Justin L. P.
Benesch
Diamond Proposal Number(s):
[12346]
Open Access
Abstract: Mechanical force–induced conformational changes in proteins underpin a variety of physiological functions, typified in muscle contractile machinery. Mutations in the actin-binding protein filamin C (FLNC) are linked to musculoskeletal pathologies characterized by altered biomechanical properties and sometimes aggregates. HspB1, an abundant molecular chaperone, is prevalent in striated muscle where it is phosphorylated in response to cues including mechanical stress. We report the interaction and up-regulation of both proteins in three mouse models of biomechanical stress, with HspB1 being phosphorylated and FLNC being localized to load-bearing sites. We show how phosphorylation leads to increased exposure of the residues surrounding the HspB1 phosphosite, facilitating their binding to a compact multidomain region of FLNC proposed to have mechanosensing functions. Steered unfolding of FLNC reveals that its extension trajectory is modulated by the phosphorylated region of HspB1. This may represent a posttranslationally regulated chaperone-client protection mechanism targeting over-extension during mechanical stress.
|
May 2019
|
|
I10-Beamline for Advanced Dichroism
|
Diamond Proposal Number(s):
[20748]
Open Access
Abstract: The recently discovered topological phase offers new possibilities for spintronics and condensed matter. Even insulating material exhibits conductivity at the edges of certain systems, giving rise to an anomalous quantum Hall effect and other coherent spin transport phenomena, in which heat dissipation is minimized, with potential uses for next-generation energy-efficient electronics. While the metallic surface states of topological insulators (TIs) have been extensively studied, direct comparison of the surface and bulk magnetic properties of TIs has been little explored. We report unambiguous evidence for distinctly enhanced surface magnetism in a prototype magnetic TI, Cr-doped Bi2Se3. Using synchrotron-based x-ray techniques, we demonstrate a “three-step transition” model, with a temperature window of ~15 K, where the TI surface is magnetically ordered while the bulk is not. Understanding the dual magnetization process has strong implications for defining a physical modelof magnetic TIs and lays the foundation for applications to information technology.
|
Feb 2019
|
|
I02-Macromolecular Crystallography
I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
|
Mark
Elliott
,
Christine
Favre-guilmard
,
Sai Man
Liu
,
Jacquie
Maignel
,
Geoffrey
Masuyer
,
Matthew
Beard
,
Christopher
Boone
,
Denis
Carré
,
Mikhail
Kalinichev
,
Stephane
Lezmi
,
Imran
Mir
,
Camille
Nicoleau
,
Shilpa
Palan
,
Cindy
Perier
,
Elsa
Raban
,
Sicai
Zhang
,
Min
Dong
,
Pal
Stenmark
,
Johannes
Krupp
Diamond Proposal Number(s):
[11265, 15806]
Open Access
Abstract: Although botulinum neurotoxin serotype A (BoNT/A) products are common treatments for various disorders, there is only one commercial BoNT/B product, whose low potency, likely stemming from low affinity toward its human receptor synaptotagmin 2 (hSyt2), has limited its therapeutic usefulness. We express and characterize two full-length recombinant BoNT/B1 proteins containing designed mutations E1191M/S1199Y (rBoNT/B1MY) and E1191Q/S1199W (rBoNT/B1QW) that enhance binding to hSyt2. In preclinical models including human-induced pluripotent stem cell neurons and a humanized transgenic mouse, this increased hSyt2 affinity results in high potency, comparable to that of BoNT/A. Last, we solve the cocrystal structure of rBoNT/B1MY in complex with peptides of hSyt2 and its homolog hSyt1. We demonstrate that neuronal surface receptor binding limits the clinical efficacy of unmodified BoNT/B and that modified BoNT/B proteins have promising clinical potential.
|
Jan 2019
|
|
Theoretical Physics
|
Fengjiao
Qian
,
Lars J.
Bannenberg
,
Heribert
Wilhelm
,
Grégory
Chaboussant
,
Lisa M.
Debeer-schmitt
,
Marcus P.
Schmidt
,
Aisha
Aqeel
,
Thomas T. M.
Palstra
,
Ekkes
Brück
,
Anton J. E.
Lefering
,
Catherine
Pappas
,
Maxim
Mostovoy
,
Andrey O.
Leonov
Open Access
Abstract: The lack of inversion symmetry in the crystal lattice of magnetic materials gives rise to complex noncollinear spin orders through interactions of a relativistic nature, resulting in interesting physical phenomena, such as emergent electromagnetism. Studies of cubic chiral magnets revealed a universal magnetic phase diagram composed of helical spiral, conical spiral, and skyrmion crystal phases. We report a remarkable deviation from this universal behavior. By combining neutron diffraction with magnetization measurements, we observe a new multidomain state in Cu2OSeO3. Just below the upper critical field at which the conical spiral state disappears, the spiral wave vector rotates away from the magnetic field direction. This transition gives rise to large magnetic fluctuations. We clarify the physical origin of the new state and discuss its multiferroic properties.
|
Sep 2018
|
|
I05-ARPES
|
Cheng
Chen
,
Meixiao
Wang
,
Jinxiong
Wu
,
Huixia
Fu
,
Haifeng
Yang
,
Zhen
Tian
,
Teng
Tu
,
Han
Peng
,
Yan
Sun
,
Xiang
Xu
,
Juan
Jiang
,
Niels B. M.
Schroeter
,
Yiwei
Li
,
Ding
Pei
,
Shuai
Liu
,
Sandy A.
Ekahana
,
Hongtao
Yuan
,
Jiamin
Xue
,
Gang
Li
,
Jinfeng
Jia
,
Zhongkai
Liu
,
Binghai
Yan
,
Hailin
Peng
,
Yulin
Chen
Diamond Proposal Number(s):
[18005]
Open Access
Abstract: Semiconductors are essential materials that affect our everyday life in the modern world. Two-dimensional semiconductors with high mobility and moderate bandgap are particularly attractive today because of their potential application in fast, low-power, and ultrasmall/thin electronic devices. We investigate the electronic structures of a new layered air-stable oxide semiconductor, Bi2O2Se, with ultrahigh mobility (~2.8 × 105 cm2/V⋅s at 2.0 K) and moderate bandgap (~0.8 eV). Combining angle-resolved photoemission spectroscopy and scanning tunneling microscopy, we mapped out the complete band structures of Bi2O2Se with key parameters (for example, effective mass, Fermi velocity, and bandgap). The unusual spatial uniformity of the bandgap without undesired in-gap states on the sample surface with up to ~50% defects makes Bi2O2Se an ideal semiconductor for future electronic applications. In addition, the structural compatibility between Bi2O2Se and interesting perovskite oxides (for example, cuprate high–transition temperature superconductors and commonly used substrate material SrTiO3) further makes heterostructures between Bi2O2Se and these oxides possible platforms for realizing novel physical phenomena, such as topological superconductivity, Josephson junction field-effect transistor, new superconducting optoelectronics, and novel lasers.
|
Sep 2018
|
|
I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I24-Microfocus Macromolecular Crystallography
|
Haigang
Song
,
Niels S.
Van Der Velden
,
Sally L.
Shiran
,
Patrick
Bleiziffer
,
Christina
Zach
,
Ramon
Sieber
,
Aman S.
Imani
,
Florian
Krausbeck
,
Markus
Aebi
,
Michael F.
Freeman
,
Sereina
Riniker
,
Markus
Künzler
,
James H.
Naismith
Open Access
Abstract: The peptide bond, the defining feature of proteins, governs peptide chemistry by abolishing nucleophilicity of the nitrogen. This and the planarity of the peptide bond arise from the delocalization of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl. While chemical methylation of an amide bond uses a strong base to generate the imidate, OphA, the precursor protein of the fungal peptide macrocycle omphalotin A, self-hypermethylates amides at pH 7 using S-adenosyl methionine (SAM) as cofactor. The structure of OphA reveals a complex catenane-like arrangement in which the peptide substrate is clamped with its amide nitrogen aligned for nucleophilic attack on the methyl group of SAM. Biochemical data and computational modeling suggest a base-catalyzed reaction with the protein stabilizing the reaction intermediate. Backbone N-methylation of peptides enhances their protease resistance and membrane permeability, a property that holds promise for applications to medicinal chemistry.
|
Aug 2018
|
|
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
|
Diamond Proposal Number(s):
[10627]
Open Access
Abstract: Toxoplasma and Plasmodium are the parasitic agents of toxoplasmosis and malaria, respectively, and use perforin-like proteins (PLPs) to invade host organisms and complete their life cycles. The Toxoplasma gondii PLP1 (TgPLP1) is required for efficient exit from parasitophorous vacuoles in which proliferation occurs. We report structures of the membrane attack complex/perforin (MACPF) and Apicomplexan PLP C-terminal β-pleated sheet (APCβ) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APCβ domain has a novel β-prism fold joined to the MACPF domain by a short linker. Molecular dynamics simulations suggest that the helical MACPF oligomer preserves a biologically important interface, whereas the APCβ domain binds preferentially through a hydrophobic loop to membrane phosphatidylethanolamine, enhanced by the additional presence of inositol phosphate lipids. This mode of membrane binding is supported by site-directed mutagenesis data from a liposome-based assay. Together, these structural and biophysical findings provide insights into the molecular mechanism of membrane targeting by TgPLP1.
|
Mar 2018
|
|
B22-Multimode InfraRed imaging And Microspectroscopy
|
Diamond Proposal Number(s):
[14590]
Open Access
Abstract: Large earthquakes occur in rocks undergoing high-pressure/low-temperature metamorphism during subduction. Rhythmic major-element zoning in garnet is a common product of such metamorphism, and one that must record a fundamental subduction process. We argue that rhythmic major-element zoning in subduction zone garnets from the Franciscan Complex, California, developed in response to growth-dissolution cycles driven by pressure pulses. Using electron probe microanalysis and novel techniques in Raman and synchrotron Fourier transform infrared microspectroscopy, we demonstrate that at least four such pressure pulses, of magnitude 100–350 MPa, occurred over less than 300,000 years. These pressure magnitude and time scale constraints are most consistent with the garnet zoning having resulted from periodic overpressure development-dissipation cycles, related to pore-fluid pressure fluctuations linked to earthquake cycles. This study demonstrates that some metamorphic reactions can track individual earthquake cycles and thereby opens new avenues to the study of seismicity.
|
Mar 2018
|
|
