Hybrid Structural Model of the Complete Human ESCRT-0 Complex

被引：65

作者：

Ren, Xuefeng ^{[1
]}

Kloer, Daniel P. ^{[1
]}

Kim, Young C. ^{[2
]}

Ghirlando, Rodolfo ^{[1
]}

Saidi, Layla F. ^{[1
]}

Hummer, Gerhard ^{[2
]}

Hurley, James H. ^{[1
]}

机构：

[1] NIDDK, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[2] NIDDK, Chem Phys Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

来源：

STRUCTURE | 2009年 / 17卷 / 03期

关键词：

UBIQUITIN-BINDING; HRS; PROTEINS; STAM; ENDOSOME; DOMAINS; LOCALIZATION; DEGRADATION; TRAFFICKING; ASSOCIATION;

D O I：

10.1016/j.str.2009.01.012

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：

The human Hrs and STAM proteins comprise the ESCRT-0 complex, which sorts ubiquitinated cell surface receptors to lysosomes for degradation. Here we report a model for the complete ESCRT-0 complex based on the crystal structure of the Hrs-STAM core complex, previously solved domain structures, hydrodynamic measurements, and Monte Carlo simulations. ESCRT-0 expressed in insect cells has a hydrodynamic radius of R-H = 7.9 nm and is a 1:1 heterodimer. The 2.3 angstrom crystal structure of the ESCRT-0 core complex reveals two domain-swapped GAT domains and an antiparallel two-stranded coiled-coil, similar to yeast ESCRT-0. ESCRT-0 typifies a class of biomolecular assemblies that combine structured and unstructured elements, and have dynamic and open conformations to ensure versatility in target recognition. Coarse-grained Monte Carlo simulations constrained by experimental R-H values for ESCRT-0 reveal a dynamic ensemble of conformations well suited for diverse functions.

引用

页码：406 / 416

页数：11

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