Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.
3D Reconstruction of Protein
Biochemistry
Protein Structure Aspects
Structural Biology
Three-Dimensional Reconstruction of Biomoleculair Structures
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
24 Jan 2020
24 Jan 2020
Historique:
received:
24
09
2019
revised:
24
11
2019
accepted:
03
12
2019
pubmed:
14
1
2020
medline:
14
1
2020
entrez:
14
1
2020
Statut:
ppublish
Résumé
The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2-infected people experience long-term viral control and survival, resembling HIV-1 elite control. HIV-2 Nef has overlapping but also distinct functions from HIV-1 Nef. Here we report the crystal structure of HIV-2 Nef core. The di-leucine sorting motif forms a helix bound to neighboring molecules, and moreover, isothermal titration calorimetry demonstrated that the CD3 endocytosis motif can directly bind to HIV-2 Nef, ensuring AP-2-mediated endocytosis for CD3. The highly conserved C-terminal region forms a α-helix, absent from HIV-1. We further determined the structure of simian immunodeficiency virus (SIV) Nef harboring this region, demonstrating similar C-terminal α-helix, which may contribute to AP-1 binding for MHC-I downregulation. These results provide insights into the distinct pathogenesis of HIV-2 infection.
Identifiants
pubmed: 31927483
pii: S2589-0042(19)30503-6
doi: 10.1016/j.isci.2019.100758
pmc: PMC6956826
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100758Subventions
Organisme : Medical Research Council
ID : MC_U190085854
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S020616/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing financial interests.
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