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

被引：301

作者：

Schur, Florian K. M. ^{[1
,2
]}

Obr, Martin ^{[2
,3
]}

Hagen, Wim J. H. ^{[1
]}

Wan, William ^{[1
]}

Jakobi, Arjen J. ^{[1
,4
]}

Kirkpatrick, Joanna M. ^{[5
,6
]}

Sachse, Carsten ^{[1
]}

Kraeusslich, Hans-Georg ^{[2
,3
]}

Briggs, John A. G. ^{[1
,2
]}

机构：

[1] European Mol Biol Lab, Struct & Computat Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany

[2] Univ Klinikum Heidelberg, European Mol Biol Lab, Mol Med Partnership Unit, Heidelberg, Germany

[3] Univ Klinikum Heidelberg, Dept Infect Dis, Virol, Neuenheimer Feld 324, D-69120 Heidelberg, Germany

[4] European Mol Biol Lab, DESY Deutsch Elekt Synchrotron, Hamburg Unit, Notkestr 85, D-22607 Hamburg, Germany

[5] European Mol Biol Lab, Prote Core Facil, Meyerhofstr 1, D-69117 Heidelberg, Germany

[6] Fritz Lipmann Inst, Leibniz Inst Aging, Beutenbergstr 11, D-07745 Jena, Germany

来源：

SCIENCE | 2016年 / 353卷 / 6298期

关键词：

TYPE-1 GAG PRECURSOR; CRYSTAL-STRUCTURES; IN-VITRO; PROTEIN; INHIBITOR; POLYPROTEIN; RESISTANCE; BEVIRIMAT; DOMAIN;

D O I：

10.1126/science.aaf9620

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Immature HIV-1 assembles at and buds from the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation can be blocked by maturation inhibitors (MIs), thereby abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation and is the target of MIs. We applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 angstrom resolution and built an atomic model. The structure reveals a network of intra-and intermolecular 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.

引用

页码：506 / 508

页数：3

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