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An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation

Immature HIV-1 assembles at, and buds from, the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation is blocked by protease and maturation inhibitors (MIs), abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag...

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Bibliographische Detailangaben
Hauptverfasser: Schur, Florian Konstantin Michael (VerfasserIn) , Obr, Martin (VerfasserIn) , Kräusslich, Hans-Georg (VerfasserIn) , Briggs, John A. G. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 14 July 2016
In: Science
Year: 2016, Jahrgang: 353, Heft: 6298, Pages: 506-508
ISSN:1095-9203
DOI:10.1126/science.aaf9620
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1126/science.aaf9620
Verlag, Volltext: http://science.sciencemag.org/content/early/2016/07/13/science.aaf9620
Volltext
Verfasserangaben:Florian K.M. Schur, Martin Obr, Wim J.H. Hagen, William Wan, Arjen J. Jakobi, Joanna M. Kirkpatrick, Carsten Sachse, Hans-Georg Kräusslich, John A.G. Briggs
Beschreibung
Zusammenfassung:Immature HIV-1 assembles at, and buds from, the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation is blocked by protease and maturation inhibitors (MIs), abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation, and the target of MIs. Here we applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 Å resolution and built an atomic model. The structure reveals a network of intra- and inter-molecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1.
Beschreibung:Gesehen am 04.01.2019
Beschreibung:Online Resource
ISSN:1095-9203
DOI:10.1126/science.aaf9620

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