Solution Structure of the ESCRT-I and -II Supercomplex: Implications for Membrane Budding and Scission

The ESCRT-I and ESCRT-II supercomplex induces membrane buds that invaginate into the lumen of endosomes, a process central to the lysosomal degradation of ubiquitinated membrane proteins. The solution conformation of the membrane-budding ESCRT-I-II supercomplex from yeast was refined against small-a...

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Published inStructure (London) Vol. 20; no. 5; pp. 874 - 886
Main Authors Boura, Evzen, Różycki, Bartosz, Chung, Hoi Sung, Herrick, Dawn Z., Canagarajah, Bertram, Cafiso, David S., Eaton, William A., Hummer, Gerhard, Hurley, James H.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 09.05.2012
Subjects
Cell Membrane - metabolism
Crescent
Crystallography, X-Ray
Degradation
Endosomal Sorting Complexes Required for Transport - chemistry
Endosomal Sorting Complexes Required for Transport - metabolism
Endosomes - metabolism
Fluorescence Resonance Energy Transfer
Mathematical models
Membranes
Models, Molecular
Protein Structure, Secondary
Saccharomyces cerevisiae - metabolism
Scattering, Small Angle
Scission
Solutions
Sorting
Spectra
Yeast
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Summary:The ESCRT-I and ESCRT-II supercomplex induces membrane buds that invaginate into the lumen of endosomes, a process central to the lysosomal degradation of ubiquitinated membrane proteins. The solution conformation of the membrane-budding ESCRT-I-II supercomplex from yeast was refined against small-angle X-ray scattering (SAXS), single-molecule Förster resonance energy transfer (smFRET), and double electron-electron resonance (DEER) spectra. These refinements yielded an ensemble of 18 ESCRT-I-II supercomplex structures that range from compact to highly extended. The crescent shapes of the ESCRT-I-II supercomplex structures provide the basis for a detailed mechanistic model, in which ESCRT-I-II stabilizes membrane buds and coordinates cargo sorting by lining the pore of the nascent bud necks. The hybrid refinement used here is general and should be applicable to other dynamic multiprotein assmeblies. [Display omitted] ► Solution structures of yeast ESCRT-II complex and ESCRT-I-II supercomplex ► ESCRT-I-II has compact, crescent-shaped, and highly extended conformations ► ESCRT-I-II crescent shapes can be docked into a model vesicle bud neck ► Model for coupling of cargo sorting, membrane budding, and membrane scission
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These authors contributed equally to this work
ISSN:0969-2126
1878-4186
DOI:10.1016/j.str.2012.03.008