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Hybrid Structural Model of the Complete Human ESCRT‐0 Complex
Author(s) -
Ren Xuefeng,
Kloer Daniel,
Kim Youngchan,
Ghirlando Rodolfo,
Saidi Layla F,
Hummer Gerhard,
Hurley James H
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.683.1
Subject(s) - escrt , antiparallel (mathematics) , endosome , chemistry , coiled coil , biophysics , physics , biology , receptor , biochemistry , quantum mechanics , magnetic field
The human Hrs and STAM proteins comprise the ESCRT‐0 complex, which has a pivotal role in directing ubiquitinated cell surface receptors to the lysosomal degradation pathway. Here we report a structural model for the complete ESCRT‐0 complex based on the high resolution structure of the Hrs‐STAM core complex, previously solved crystal and solution structures, hydrodynamic measurements, and coarse‐grained Monte Carlo simulations. Recombinant ESCRT‐0 expressed in insect cells has a hydrodynamic radius of RH = 7.9 nm and is a 1:1 heterodimer. The 2.3 Åcrystal structure of the ESCRT‐0 core complex reveals two domain‐swapped GAT domains and an antiparallel twostranded coiled‐coil, similar to the core of yeast ESCRT‐0. Coarse‐grained Monte Carlo simulations constrained by experimental RH values for full‐length ESCRT‐0 reveal a dynamic ensemble of conformations well‐suited for the diverse functions of the complex.ESCRT‐0 typifies a class of biomolecular assemblies that combine both structured andunstructured elements, and have overall dynamic and open conformations to ensure versatility in target recognition and function. The multipronged approach used here, combining experiments and simulations at different levels of resolution, should be useful whenever the complexes are only partially structured. This research was supported by NIH intramural support, NIDDK (J.H.H. and G.H.) and IATAP (J.H.H.).