scholarly journals In situ structure and organization of the influenza C virus surface glycoprotein

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Steinar Halldorsson ◽  
Kasim Sader ◽  
Jack Turner ◽  
Lesley J. Calder ◽  
Peter B. Rosenthal
Keyword(s):  
Membrane Fusion ◽  
Hexagonal Lattice ◽  
Surface Glycoprotein ◽  
Structural Basis ◽  
Virus Surface ◽  
The Matrix ◽  
Influenza C Virus ◽  
Subtomogram Averaging ◽  
Electron Cryotomography

AbstractThe lipid-enveloped influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion at the low pH of the endosome. Here we apply electron cryotomography and subtomogram averaging to describe the structural basis for hexagonal lattice formation by HEF on the viral surface. The conformation of the glycoprotein in situ is distinct from the structure of the isolated trimeric ectodomain, showing that a splaying of the membrane distal domains is required to mediate contacts that form the lattice. The splaying of these domains is also coupled to changes in the structure of the stem region which is involved in membrane fusion, thereby linking HEF’s membrane fusion conformation with its assembly on the virus surface. The glycoprotein lattice can form independent of other virion components but we show a major role for the matrix layer in particle formation.

scholarly journals Helical arrays of U-shaped ATP synthase dimers form tubular cristae in ciliate mitochondria

2016 ◽  
Vol 113 (30) ◽  
pp. 8442-8447 ◽  
Author(s):  
Alexander W. Mühleip ◽  
Friederike Joos ◽  
Christoph Wigge ◽  
Achilleas S. Frangakis ◽  
Werner Kühlbrandt ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Protein Complexes ◽  
Paramecium Tetraurelia ◽  
Mitochondrial Atp Synthase ◽  
Structural Differences ◽  
Membrane Protein Complexes ◽  
Subtomogram Averaging ◽  
Electron Cryotomography ◽  
Energy Converting

F1Fo-ATP synthases are universal energy-converting membrane protein complexes that synthesize ATP from ADP and inorganic phosphate. In mitochondria of yeast and mammals, the ATP synthase forms V-shaped dimers, which assemble into rows along the highly curved ridges of lamellar cristae. Using electron cryotomography and subtomogram averaging, we have determined the in situ structure and organization of the mitochondrial ATP synthase dimer of the ciliate Paramecium tetraurelia. The ATP synthase forms U-shaped dimers with parallel monomers. Each complex has a prominent intracrista domain, which links the c-ring of one monomer to the peripheral stalk of the other. Close interaction of intracrista domains in adjacent dimers results in the formation of helical ATP synthase dimer arrays, which differ from the loose dimer rows in all other organisms observed so far. The parameters of the helical arrays match those of the cristae tubes, suggesting the unique features of the P. tetraurelia ATP synthase are directly responsible for generating the helical tubular cristae. We conclude that despite major structural differences between ATP synthase dimers of ciliates and other eukaryotes, the formation of ATP synthase dimer rows is a universal feature of mitochondria and a fundamental determinant of cristae morphology.

scholarly journals Cryo-ET analysis of budding yeast synaptonemal complexes in situ

2019 ◽  
Author(s):  
Olivia X. Ma ◽  
Shujun Cai ◽  
Jian Shi ◽  
Lu Gan
Keyword(s):  
Triple Helix ◽  
Phase Contrast ◽  
Central Element ◽  
Super Resolution ◽  
Native Structure ◽  
Homologous Chromosomes ◽  
Triple Helices ◽  
Subtomogram Averaging ◽  
Electron Cryotomography

ABSTRACTThe synaptonemal complex (SC) is the large, conserved, proteinaceous scaffold that assembles between and holds together homologous chromosomes in meiotic prophase. Knowledge of the native structure of this complex is needed to evaluate how the SC carries out its functions. Traditional electron microscopy and super-resolution light microscopy have revealed that in many organisms, the SC has a ladder-like structure: two rail-like lateral elements are bridged by a set of rung-like transverse filaments. The transverse filaments are connected along their centers by a central element. To determine the 3-D architecture of the SC in situ, we studied frozen-hydrated meiotic yeast cell cryosections by Volta phase-contrast electron cryotomography and subtomogram analysis. We find the SC is built from triple-helical filaments that pack into dense polycrystalline bundles. These structures are also abundant in the polycomplexes of pachytene-arrested cells. Dissolution by 1,6-hexanediol treatment suggests that these triple-helical filaments belong to the central region of the SCs. Subtomogram averaging revealed that the SC’s triple-helical filaments are up to 12-nm thick and have a 5-nm rise and 130-nm pitch. Single triple-helices and polymers thinner than the triple helix, such as single or double strands, were not detected, consistent with the strong self-oligomerization properties of SC proteins. The dense packing of SC subunits supports the notion that the SC’s mechanical properties help coordinate the rapid end-to-end communication across synapsed chromosomes.

Microdiffraction analysis of precipitate crystallography and morphology in Al alloys

1990 ◽  
Vol 48 (4) ◽  
pp. 954-955
Author(s):  
B.C. Muddle ◽  
G.R. Hugo
Keyword(s):  
Point Group ◽  
Hexagonal Lattice ◽  
Intersection Point ◽  
Saed Pattern ◽  
Point Symmetry ◽  
Hexagonal Symmetry ◽  
Precipitate Crystal ◽  
The Matrix ◽  
The Subject ◽  
Electron Microdiffraction

Electron microdiffraction has been used to determine the crystallography of precipitation in Al-Cu-Mg-Ag and Al-Ge alloys for individual precipitates with dimensions down to 10 nm. The crystallography has been related to the morphology of the precipitates using an analysis based on the intersection point symmetry. This analysis requires that the precipitate form be consistent with the intersection point group, defined as those point symmetry elements common to precipitate and matrix crystals when the precipitate crystal is in its observed orientation relationship with the matrix.In Al-Cu-Mg-Ag alloys with high Cu:Mg ratios and containing trace amounts of silver, a phase designated Ω readily precipitates as thin, hexagonal-shaped plates on matrix {111}α planes. Examples of these precipitates are shown in Fig. 1. The structure of this phase has been the subject of some controversy. An SAED pattern, Fig. 2, recorded from matrix and precipitates parallel to a <11l>α axis is suggestive of hexagonal symmetry and a hexagonal lattice has been proposed on the basis of such patterns.

Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors

2003 ◽  
Vol 70 ◽  
pp. 201-212 ◽  
Author(s):  
Hideaki Nagase ◽  
Keith Brew
Keyword(s):  
Three Dimensional ◽  
Therapeutic Interventions ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Structural Basis ◽  
Structural Elements ◽  
Ridge Structure ◽  
Extracellular Matrix Components ◽  
Metalloproteinase Inhibitors ◽  
The Matrix ◽  
A Disintegrin And Metalloproteinase

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs), enzymes that play central roles in the degradation of extracellular matrix components. The balance between MMPs and TIMPs is important in the maintenance of tissues, and its disruption affects tissue homoeostasis. Four related TIMPs (TIMP-1 to TIMP-4) can each form a complex with MMPs in a 1:1 stoichiometry with high affinity, but their inhibitory activities towards different MMPs are not particularly selective. The three-dimensional structures of TIMP-MMP complexes reveal that TIMPs have an extended ridge structure that slots into the active site of MMPs. Mutation of three separate residues in the ridge, at positions 2, 4 and 68 in the amino acid sequence of the N-terminal inhibitory domain of TIMP-1 (N-TIMP-1), separately and in combination has produced N-TIMP-1 variants with higher binding affinity and specificity for individual MMPs. TIMP-3 is unique in that it inhibits not only MMPs, but also several ADAM (a disintegrin and metalloproteinase) and ADAMTS (ADAM with thrombospondin motifs) metalloproteinases. Inhibition of the latter groups of metalloproteinases, as exemplified with ADAMTS-4 (aggrecanase 1), requires additional structural elements in TIMP-3 that have not yet been identified. Knowledge of the structural basis of the inhibitory action of TIMPs will facilitate the design of selective TIMP variants for investigating the biological roles of specific MMPs and for developing therapeutic interventions for MMP-associated diseases.

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

scholarly journals Supramolecular ionic polymer/carbon nanotube composite hydrogels with enhanced electromechanical performance

2020 ◽  
Vol 9 (1) ◽  
pp. 478-488 ◽  
Author(s):  
Yun-Fei Zhang ◽  
Fei-Peng Du ◽  
Ling Chen ◽  
Ka-Wai Yeung ◽  
Yuqing Dong ◽  
...  
Keyword(s):  
Carbon Nanotube ◽  
Ion Mobility ◽  
Artificial Muscles ◽  
Ionic Polymer ◽  
Composite Hydrogels ◽  
The Matrix ◽  
Electromechanical Performance ◽  
Carbon Nanotube Composite ◽  
Robotic Devices

AbstractElectroactive hydrogels have received increasing attention due to the possibility of being used in biomimetics, such as for soft robotics and artificial muscles. However, the applications are hindered by the poor mechanical properties and slow response time. To address these issues, in this study, supramolecular ionic polymer–carbon nanotube (SIPC) composite hydrogels were fabricated via in situ free radical polymerization. The polymer matrix consisted of carbon nanotubes (CNTs), styrene sulfonic sodium (SSNa), β-cyclodextrin (β-CD)-grafted acrylamide, and ferrocene (Fc)-grafted acrylamide, with the incorporation of SSNa serving as the ionic source. On applying an external voltage, the ions accumulate on one side of the matrix, leading to localized swelling and bending of the structure. Therefore, a controllable and reversible actuation can be achieved by changing the applied voltage. The tensile strength of the SIPC was improved by over 300%, from 12 to 49 kPa, due to the reinforcement effect of the CNTs and the supramolecular host–guest interactions between the β-CD and Fc moieties. The inclusion of CNTs not only improved the tensile properties but also enhanced the ion mobility, which lead to a faster electromechanical response. The presented electro-responsive composite hydrogel shows a high potential for the development of robotic devices and soft smart components for sensing and actuating applications.

scholarly journals Hexagonal-Shaped Spin Crossover Nanoparticles Studied by Ising-Like Model Solved by Local Mean Field Approximation

2021 ◽  
Vol 7 (5) ◽  
pp. 69
Author(s):  
Catherine Cazelles ◽  
Jorge Linares ◽  
Mamadou Ndiaye ◽  
Pierre-Richard Dahoo ◽  
Kamel Boukheddaden
Keyword(s):  
Spin Crossover ◽  
Hexagonal Lattice ◽  
Mean Field ◽  
Field Approximation ◽  
Mean Field Approximation ◽  
Ligand Field ◽  
Order And Disorder ◽  
The Matrix ◽  
Local Mean ◽  
Parameter Values

The properties of spin crossover (SCO) nanoparticles were studied for five 2D hexagonal lattice structures of increasing sizes embedded in a matrix, thus affecting the thermal properties of the SCO region. These effects were modeled using the Ising-like model in the framework of local mean field approximation (LMFA). The systematic combined effect of the different types of couplings, consisting of (i) bulk short- and long-range interactions and (ii) edge and corner interactions at the surface mediated by the matrix environment, were investigated by using parameter values typical of SCO complexes. Gradual two and three hysteretic transition curves from the LS to HS states were obtained. The results were interpreted in terms of the competition between the structure-dependent order and disorder temperatures (TO.D.) of internal coupling origin and the ligand field-dependent equilibrium temperatures (Teq) of external origin.

scholarly journals Prefusion structure of human cytomegalovirus glycoprotein B and structural basis for membrane fusion

2021 ◽  
Vol 7 (10) ◽  
pp. eabf3178
Author(s):  
Yuhang Liu ◽  
Kyle P. Heim ◽  
Ye Che ◽  
Xiaoyuan Chi ◽  
Xiayang Qiu ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Human Cytomegalovirus ◽  
Transmembrane Domain ◽  
Proximal Region ◽  
Viral Envelope ◽  
Vaccine Antigen ◽  
Glycoprotein B ◽  
Structural Basis ◽  
Fusion Inhibitor ◽  
Host Cell Membrane

Human cytomegalovirus (HCMV) causes congenital disease with long-term morbidity. HCMV glycoprotein B (gB) transitions irreversibly from a metastable prefusion to a stable postfusion conformation to fuse the viral envelope with a host cell membrane during entry. We stabilized prefusion gB on the virion with a fusion inhibitor and a chemical cross-linker, extracted and purified it, and then determined its structure to 3.6-Å resolution by electron cryomicroscopy. Our results revealed the structural rearrangements that mediate membrane fusion and details of the interactions among the fusion loops, the membrane-proximal region, transmembrane domain, and bound fusion inhibitor that stabilized gB in the prefusion state. The structure rationalizes known gB antigenic sites. By analogy to successful vaccine antigen engineering approaches for other viral pathogens, the high-resolution prefusion gB structure provides a basis to develop stabilized prefusion gB HCMV vaccine antigens.

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