Structural analysis and modeling reveals new mechanisms governing ESCRT-III spiral filament assembly

© 2014 Shen et al..

The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ESCRT-III (endosomal sorting complex required for transport III) filaments mediate membrane scission during the ostensibly disparate processes of multivesicular endosome biogenesis, cytokinesis, and retroviral budding. However, mechanisms by which ESCRT-III subunits assemble into a polymer remain unknown. Using cryogenic electron microscopy (cryo-EM), we found that the full-length ESCRT-III subunit Vps32/CHMP4B spontaneously forms single-stranded spiral filaments. The resolution afforded by two-dimensional cryo-EM combined with molecular dynamics simulations revealed that individual Vps32/CHMP4B monomers within a filament are flexible and able to accommodate a range of bending angles. In contrast, the interface between monomers is stable and refractory to changes in conformation. We additionally found that the carboxyl terminus of Vps32/CHMP4B plays a key role in restricting the lateral association of filaments. Our findings highlight new mechanisms by which ESCRT-III filaments assemble to generate a unique polymer capable of membrane remodeling in multiple cellular contexts.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:206

Enthalten in:

The Journal of cell biology - 206(2014), 6 vom: 15. Sept., Seite 763-77

Sprache:

Englisch

Beteiligte Personen:

Shen, Qing-Tao [VerfasserIn]
Schuh, Amber L [VerfasserIn]
Zheng, Yuqing [VerfasserIn]
Quinney, Kyle [VerfasserIn]
Wang, Lei [VerfasserIn]
Hanna, Michael [VerfasserIn]
Mitchell, Julie C [VerfasserIn]
Otegui, Marisa S [VerfasserIn]
Ahlquist, Paul [VerfasserIn]
Cui, Qiang [VerfasserIn]
Audhya, Anjon [VerfasserIn]

Links:

Volltext

Themen:

Endosomal Sorting Complexes Required for Transport
Journal Article
Polymers
Protein Subunits
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Anmerkungen:

Date Completed 18.11.2014

Date Revised 21.10.2021

published: Print-Electronic

PDB: 2GD5

Citation Status MEDLINE

doi:

10.1083/jcb.201403108

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM241719240