Academic Journal
Binding stoichiometry and structural model of the HIV-1 Rev/Importin β complex
| العنوان: | Binding stoichiometry and structural model of the HIV-1 Rev/Importin β complex |
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| المؤلفون: | Spittler, Didier, Indorato, Rose-Laure, Erba, Elisabetta Boeri, Delaforge, Elise, Signor, Luca, Harris, Simon, Garcia-Saez, Isabel, Palencia, Andrés, Gabel, Frank, Blackledge, Martin, Noirclerc-Savoye, Marjolaine, Petosa, Carlo |
| المساهمون: | Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Groupe Épigénétique et voies moléculaires / Epigenetics and Molecular Pathways Group (IBS-EPIGEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017) |
| المصدر: | Life Science Alliance ; https://hal.science/hal-03453423 ; Life Science Alliance, 2022, ⟨10.26508/lsa.202201431⟩ |
| بيانات النشر: | CCSD |
| سنة النشر: | 2022 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | HIV-1 Rev, Importin β, nuclear transport, molecular docking, protein-protein interactions, binding studies, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases |
| الوصف: | International audience ; ABSTRACT HIV-1 Rev mediates the nuclear export of intron-containing viral RNA transcripts and is essential for viral replication. Rev is imported into the nucleus by the host protein Importin β (Impβ), but how Rev associates with Impβ is poorly understood. Here, we report biochemical, mutational, and biophysical studies of the Impβ/Rev complex. We show that Impβ binds two Rev monomers through independent binding sites, in contrast to the 1:1 binding stoichiometry observed for most Impβ cargos. Peptide scanning data and charge-reversal mutations identify the N-terminal tip of Rev helix α2 within Rev’s arginine-rich motif (ARM) as a primary Impβ-binding epitope. Cross-linking mass spectrometry and compensatory mutagenesis data combined with molecular docking simulations suggest a structural model in which one Rev monomer binds to the C-terminal half of Impβ with Rev helix α2 roughly parallel to the HEAT-repeat superhelical axis, whereas the other monomer binds to the N-terminal half. These findings shed light on the molecular basis of Rev recognition by Impβ and highlight an atypical binding behavior that distinguishes Rev from canonical cellular Impβ cargos. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | BIORXIV: 2021.11.16.468785 |
| DOI: | 10.26508/lsa.202201431 |
| الاتاحة: | https://hal.science/hal-03453423 https://hal.science/hal-03453423v2/document https://hal.science/hal-03453423v2/file/2022_LifeSciAlliance_Spittler.pdf https://doi.org/10.26508/lsa.202201431 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.3A56FA04 |
| قاعدة البيانات: | BASE |
| DOI: | 10.26508/lsa.202201431 |
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