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Structure and function of the ESCRT-II-III interface in multivesicular body biogenesis
Young Jun Im1, Thomas Wollert, Evzen Boura
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Developmental Cell
|August 19, 2009
Summary
The ESCRT-II-ESCRT-III interaction, involving VPS25 and VPS20, drives vesicle formation in multivesicular bodies. This structural insight reveals how ESCRT-II activates ESCRT-III for efficient cargo sorting and budding.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- The ESCRT (Endosomal Sorting Complexes Required for Transport) machinery is crucial for multivesicular body (MVB) formation.
- ESCRT-II and ESCRT-III complexes collaborate to sort ubiquitinated cargo and mediate vesicle budding and scission.
Purpose of the Study:
- To elucidate the structural basis of the ESCRT-II and ESCRT-III interaction.
- To understand the role of this interaction in cargo sorting and vesicle formation.
Main Methods:
- X-ray crystallography to determine the structure of the ESCRT-II-ESCRT-III complex.
- Biochemical assays to assess binding affinities and functional activity.
- In vivo studies to evaluate the role of specific residues in cargo sorting.
Main Results:
- The interaction interface was mapped to VPS25 (ESCRT-II) and VPS20 (ESCRT-III).
- The crystal structure revealed specific residues critical for ESCRT-II-VPS20 interaction and ESCRT-III activation.
- ESCRT-II directly stimulates ESCRT-III-mediated vesicle budding and scission in vitro.
- VPS20 and ESCRT-II exhibit high membrane affinity, independent of ESCRT-II binding for VPS20 recruitment.
- The supercomplex structure suggests a role in inducing negative membrane curvature.
Conclusions:
- The ESCRT-II-VPS20 interaction is essential for specific cargo sorting and MVB biogenesis.
- ESCRT-II acts as a direct activator of ESCRT-III for vesicle budding and scission.
- Structural insights provide a mechanistic understanding of ESCRT-mediated membrane remodeling.
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