Structural studies on the membrane-bound immunoglobulin E (IgE)-receptor complex. 2. Mapping of distances between sites on IgE and the membrane surface

Biochemistry ◽  
1983 ◽  
Vol 22 (14) ◽  
pp. 3475-3484 ◽  
Author(s):  
David Holowka ◽  
Barbara Baird
Keyword(s):  
Immunoglobulin E ◽  
Membrane Surface ◽  
Receptor Complex ◽  
Structural Studies ◽  
Ige Receptor ◽  
Membrane Bound

Opportunistic yeast pathogen Candida spp.: Secreted and membrane-bound virulence factors

2021 ◽  
Author(s):  
Si Jie Lim ◽  
Mohd Shukuri Mohamad Ali ◽  
Suriana Sabri ◽  
Noor Dina Muhd Noor ◽  
Abu Bakar Salleh ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Drug Targets ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Host Immune System ◽  
Structural Studies ◽  
Candida Spp ◽  
Structural Investigations ◽  
Membrane Bound ◽  
Aspartyl Proteinases

Abstract Candidiasis is a fungal infection caused by Candida spp. especially Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Although the medicinal therapeutic strategies have rapidly improved, the mortality rate due to candidiasis has continuously increased. The secreted and membrane-bound virulence factors (VFs) are responsible for fungal invasion, damage and translocation through the host enterocytes besides the evasion from host immune system. VFs such as agglutinin-like sequences (Als), heat shock protein 70, phospholipases, secreted aspartyl proteinases (Sap), lipases, enolases and phytases are mostly hydrolases which degrade the enterocyte membrane components except for candidalysin, the VF acts as a peptide toxin to induce necrotic cell lysis. To date, structural studies of the VFs remain underexplored, hindering their functional analyses. Among the VFs, only secreted aspartyl proteinases and agglutinin-like sequences have their structures deposited in Protein Data Bank (PDB). Therefore, this review scrutinizes the mechanisms of these VFs by discussing the VF-deficient studies of several Candida spp. and their abilities to produce these VFs. Nonetheless, their latest reported sequential and structural analyses are discussed to impart a wider perception of the host-pathogen interactions and potential vaccine or antifungal drug targets. This review signifies that more VFs structural investigations and mining in the emerging Candida spp. are required to decipher their pathogenicity and virulence mechanisms compared to the prominent C. albicans. Lay Abstract Candida virulence factors (VFs) including mainly enzymes and proteins play vital roles in breaching the human intestinal barrier and causing deadly candidiasis. Limited VFs’ structural studies hinder deeper comprehension of their mechanisms and thus the design of vaccines and antifungal drugs against fungal infections.

NMR-Structural Studies of Membrane Bound Peptides and Proteins

1991 ◽  
pp. 109-124 ◽  
Author(s):  
Ki-Joon Shon ◽  
Patricia Schrader ◽  
Yongae Kim ◽  
Burkhard Bechinger ◽  
Michael Zasloff ◽  
...  
Keyword(s):  
Structural Studies ◽  
Membrane Bound

scholarly journals Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Kavita Singh ◽  
Martin Burkhardt ◽  
Sofia Nakuchima ◽  
Raul Herrera ◽  
Olga Muratova ◽  
...  
Keyword(s):  
Membrane Surface ◽  
Structure And Function ◽  
Fab Fragment ◽  
Membrane Anchor ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Membrane Bound ◽  
And Function ◽  
Transmission Blocking Vaccine

AbstractProteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45. 4F12 appears to sterically interfere with Pfs230 function. Combining mAbs against different epitopes of Pfs230D1 or of Pfs230D1 and Pfs48/45, significantly increased TB activity. These studies elucidate a mechanism of action of the Pfs230D1 vaccine, model the functional activity induced by a polyclonal antibody response and support the development of TB vaccines targeting Pfs230D1 and Pfs230D1-Pfs48/45.

Copper and nickel uptake and accumulation, and their effects on redox and electrical potentials of hepatopancreatic cells of Oniscus asellus Linnaeus (Porcellionidae, Isopoda)

1990 ◽  
Vol 68 (4) ◽  
pp. 651-655 ◽  
Author(s):  
M. A. Alikhan ◽  
V. Storch
Keyword(s):  
Catalytic Activity ◽  
Cell Membrane ◽  
Membrane Surface ◽  
Dry Weight ◽  
Body Tissue ◽  
Electrical Potentials ◽  
Nickel Uptake ◽  
Membrane Bound ◽  
Total Body ◽  
Cell Membrane Surface

Highest tissue Cu concentrations (1728 μg∙g dry weight−1) in whole Oniscus asellus, reared for 7 days on carrot powder containing 50 μg Cu∙g dry weight−1, 10 μg Ni∙g dry weight−1, or a mixture of 50 μg Cu and 10 μg Ni∙g dry weight−1, were observed in isopods on 50 μg Cu∙g dry weight−1, and lowest (917 μg∙g dry weight−1) in those on 10 μg Ni∙g dry weight−1. Highest Ni concentrations (277 and 272 μg∙g dry weight−1) were present in isopods fed on a mixture of 50 μg Cu and 10 μg Ni∙g dry weight−1 and 10 μg Ni∙g dry weight−1, respectively, and lowest (201 μg∙g dry weight−1) in those on 50 μg Cu∙g dry weight−1. Of the total body-tissue Cu, 8–66% was contained in membrane-bound vesicles of hepatopancreatic S-cells, and 73–89% of Ni was present inside the lumen and within S-cells of the hepatopancreas. The presence of Ni in the diet appeared to adversely affect the absorption and hepatopancreatic storage of Cu. Copper slightly enhanced, and nickel drastically reduced, the hepatopancreatic redox (= catalytic activity) and cell-membrane surface potentials. The significance of these findings is discussed.

scholarly journals Reaction–diffusion basis of retroviral infectivity

2016 ◽  
Vol 374 (2080) ◽  
pp. 20160148 ◽  
Author(s):  
S. Kashif Sadiq
Keyword(s):  
Chemical Reactions ◽  
Membrane Surface ◽  
Reaction Diffusion ◽  
Coarse Graining ◽  
Coarse Grained ◽  
Multiscale Approach ◽  
The Matrix ◽  
Membrane Bound ◽  
Spatio Temporal ◽  
Dynamics Simulations

Retrovirus particle (virion) infectivity requires diffusion and clustering of multiple transmembrane envelope proteins (Env 3 ) on the virion exterior, yet is triggered by protease-dependent degradation of a partially occluding, membrane-bound Gag polyprotein lattice on the virion interior. The physical mechanism underlying such coupling is unclear and only indirectly accessible via experiment. Modelling stands to provide insight but the required spatio-temporal range far exceeds current accessibility by all-atom or even coarse-grained molecular dynamics simulations. Nor do such approaches account for chemical reactions, while conversely, reaction kinetics approaches handle neither diffusion nor clustering. Here, a recently developed multiscale approach is considered that applies an ultra-coarse-graining scheme to treat entire proteins at near-single particle resolution, but which also couples chemical reactions with diffusion and interactions. A model is developed of Env 3 molecules embedded in a truncated Gag lattice composed of membrane-bound matrix proteins linked to capsid subunits, with freely diffusing protease molecules. Simulations suggest that in the presence of Gag but in the absence of lateral lattice-forming interactions, Env 3 diffuses comparably to Gag-absent Env 3 . Initial immobility of Env 3 is conferred through lateral caging by matrix trimers vertically coupled to the underlying hexameric capsid layer. Gag cleavage by protease vertically decouples the matrix and capsid layers, induces both matrix and Env 3 diffusion, and permits Env 3 clustering. Spreading across the entire membrane surface reduces crowding, in turn, enhancing the effect and promoting infectivity. This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.

scholarly journals Ultrastructural, cytochemical, and membrane surface marker characteristics of the atypical lymphocytes in infectious mononucleosis

Blood ◽  
1977 ◽  
Vol 50 (3) ◽  
pp. 505-515
Author(s):  
RW McKenna ◽  
J Parkin ◽  
KJ Gajl-Peczalska ◽  
JH Kersey ◽  
RD Brunning
Keyword(s):  
T Lymphocytes ◽  
Infectious Mononucleosis ◽  
Membrane Surface ◽  
Lymphocyte Activation ◽  
Surface Marker ◽  
Absolute Increase ◽  
Cytoplasmic Inclusions ◽  
Specific Subset ◽  
Membrane Bound ◽  
Acute Infectious Mononucleosis

Atypical lymphocytes from nine young adults with acute infectious mononucleosis (IM) were studied for morphologic, ultrastructural, cytochemical, and membrane surface marker characteristics. There was an absolute increase in T lymphocytes in the patients. Atypical lymphocytes accounted for 83%-96% of the lymphocyte population. These lymphocytes contained cytoplasmic inclusions which ranged in size from 1000 to 6000 A, were usually membrane bound, and consisted of parallel arrays of microtubulelike structures. The inclusions, which have been referred to as parallel tubular arrays (PTA), were found in 15%-75% of the lymphocytes from the IM patients. Ultrastructural cytochemical methods demonstrated acid phosphatase activity within many of the membrane-bound PTA. The function of the PTA is unknown. Since they were observed only in the lymphocytes which appeared to correspond to the atypical lymphocytes on light microscopy, the majority of which typed as T cells, there appears to be an association between PTA and T lymphocytes. It is possible that PTA identify a specific subset of T lymphocytes which is expanded in IM. Alternatively, PTA may be a transient finding in lymphocytes appearing only in certain biologic states of the cell such as during T-lymphocyte activation.

scholarly journals Structural basis of adenylyl cyclase 9 activation

2021 ◽  
Author(s):  
Chao Qi ◽  
Pia Lavriha ◽  
Ved Mehta ◽  
Basavraj Khanppnavar ◽  
Inayathulla Mohammed ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Binding Site ◽  
Adenylyl Cyclase ◽  
Conformational Changes ◽  
Structural Basis ◽  
Structural Studies ◽  
Nucleotide Analogue ◽  
C Terminus ◽  
Membrane Bound ◽  
A Site

Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. Although our recent structural studies of the AC9-Gαs complex provided the framework for understanding AC9 autoinhibition, the conformational changes that AC9 undergoes in response to activator binding remains poorly understood. Here, we present the cryo-EM structures of AC9 in several distinct states: (i) AC9 bound to a nucleotide inhibitor MANT-GTP, (ii) bound to an artificial activator (DARPin C4) and MANT-GTP, (iii) bound to DARPin C4 and a nucleotide analogue ATPαS, (iv) bound to Gαs and MANT-GTP. The artificial activator DARPin C4 partially activates AC9 by binding at a site that overlaps with the Gαs binding site. Together with the previously observed occluded and forskolin-bound conformations, structural comparisons of AC9 in the four new conformations show that secondary structure rearrangements in the region surrounding the forskolin binding site are essential for AC9 activation.

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