Biochemistry and Pharmacology - Research Publications

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Author: Kazemi, Mohsen × End date: 2020 × Start date: 2018 × Type: Journal Article ×

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    Scipion web tools: Easy to use cryo-EM image processing over the web
    Conesa Mingo, P ; Gutierrez, J ; Quintana, A ; de la Rosa Trevin, JM ; Zaldivar-Peraza, A ; Cuenca Alba, J ; Kazemi, M ; Vargas, J ; del Cano, L ; Segura, J ; Sorzano, COS ; Maria Carazo, J (WILEY, 2018-01)
    Macromolecular structural determination by Electron Microscopy under cryogenic conditions is revolutionizing the field of structural biology, interesting a large community of potential users. Still, the path from raw images to density maps is complex, and sophisticated image processing suites are required in this process, often demanding the installation and understanding of different software packages. Here, we present Scipion Web Tools, a web-based set of tools/workflows derived from the Scipion image processing framework, specially tailored to nonexpert users in need of very precise answers at several key stages of the structural elucidation process.
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    An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity
    Alsahafi, N ; Bakouche, N ; Kazemi, M ; Richard, J ; Ding, S ; Bhattacharyya, S ; Das, D ; Anand, SP ; Prevost, J ; Tolbert, WD ; Lu, H ; Medjahed, H ; Gendron-Lepage, G ; Delgado, GGO ; Kirk, S ; Melillo, B ; Mothes, W ; Sodroski, J ; Smith, AB ; Kaufmann, DE ; Wu, X ; Pazgier, M ; Rouiller, I ; Finzi, A ; Munro, JB (CELL PRESS, 2019-04-10)
    The HIV-1 envelope glycoprotein (Env) (gp120-gp41)3 is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible, sampling different conformational states. Before engaging CD4, Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2), followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting the conserved gp120 inner domain and mediating ADCC. Sera from HIV+ individuals contain these antibodies, which can stabilize Env State 2A in combination with CD4mc. Additionally, triggering State 2A on HIV-infected primary CD4+ T cells exposes epitopes that induce ADCC. Strategies that induce this Env conformation may represent approaches to fight HIV-1 infection.
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    Improving 3D reconstructions of macromolecular conformations
    Kazemi, M ; Sorzano, COS ; Georges, AD ; Carazo, JM ; Vargas, J (INT UNION CRYSTALLOGRAPHY, 2018-07)