A Crescent-Shaped ALIX Dimer Targets ESCRT-III CHMP4 Filaments

被引：110

作者：

Pires, Ricardo ^{[1
]}

Hartlieb, Bettina ^{[1
]}

Signor, Luca ^{[2
]}

Schoehn, Guy ^{[1
,2
]}

Lata, Suman ^{[1
]}

Roessle, Manfred ^{[3
]}

Moriscot, Christine ^{[1
,2
]}

Popov, Sergei ^{[4
]}

Hinz, Andreas ^{[1
]}

Jamin, Marc ^{[1
]}

Boyer, Veronique ^{[1
]}

Sadoul, Remy ^{[5
,6
]}

Forest, Eric ^{[2
]}

Svergun, Dmitri I. ^{[3
]}

Goettlinger, Heinrich G. ^{[4
]}

Weissenhorn, Winfried ^{[1
]}

机构：

[1] Univ Grenoble 1, EMBL, CNRS, UVHCI UMI 3265, F-38042 Grenoble 9, France

[2] UJF, CNRS, CEA, Inst Biol Struct,UMR 5075, F-38027 Grenoble 01, France

[3] European Mol Biol Lab, D-22603 Hamburg, Germany

[4] Univ Massachusetts, Sch Med, Program Mol Med, Program Gene Funct & Express, Worcester, MA 01605 USA

[5] INSERM, Grenoble Inst Neurosci, Unit 387, F-38043 Grenoble, France

[6] Univ Grenoble 1, F-38043 Grenoble, France

来源：

STRUCTURE | 2009年 / 17卷 / 06期

关键词：

RECEPTOR DOWN-REGULATION; STRUCTURAL BASIS; LATE-DOMAIN; CRYSTAL-STRUCTURE; BINDING PARTNER; PROTEIN ALIX; HIV-1; P6; ALIX/AIP1; APOPTOSIS; COMPLEX;

D O I：

10.1016/j.str.2009.04.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ALIX recruits ESCRT-III CHMP4 and is involved in membrane remodeling during endosomal receptor sorting, budding of some enveloped viruses, and cytokinesis. We show that ALIX dimerizes via the middle domain (ALIX(-V)) in solution. Structural modeling based on small angle X-ray scattering (SAXS) data reveals an elongated crescent-shaped conformation for dimeric ALIX lacking the proline-rich domain (ALIX(BRO1-V)). Mutations at the dimerization interface prevent dimerization and induce an open elongated monomeric conformation of ALIX(-V) as determined by SAXS modeling. ALIX dimerizes in vivo and dimeric ALIX colocalizes with CHMP4B upon coexpression. We show further that ALIX dimerization affects HIV-1 budding. C-terminally truncated activated CHMP4B retaining the ALIX binding site forms linear, circular, and helical filaments in vitro, which can be bridged by ALIX. Our data suggest that dimeric ALIX represents the active form that interacts with ESCRT-III CHMP4 polymers and functions as a scaffolding protein during membrane remodeling processes.

引用

页码：843 / 856

页数：14

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