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

• Verfasst von: Schur, Florian Konstantin Michael [VerfasserIn]
• Verfasst von: Obr, Martin [VerfasserIn]
• Verfasst von: Kräusslich, Hans-Georg [VerfasserIn]
• Verfasst von: Briggs, John A. G. [VerfasserIn]
• Titel: An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation
• Verf.angabe: 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
• E-Jahr: 2016
• Jahr: 14 July 2016
• Umfang: 3 S.
• Teil: volume:353
• Teil: year:2016
• Teil: number:6298
• Teil: pages:506-508
• Teil: extent:3
• Fussnoten: Gesehen am 04.01.2019
• Titel Quelle: Enthalten in: Science
• Ort Quelle: Washington, DC [u.a.] : American Association for the Advancement of Science, 1880
• Jahr Quelle: 2016
• Band/Heft Quelle: 353(2016), 6298, Seite 506-508
• ISSN Quelle: 1095-9203
• DOI: doi:10.1126/science.aaf9620
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1585933716

Abstract

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.