Cryo-EM Structure of Dodecameric Vps4p and Its 2:1 Complex with Vta1p
Abstract
The type I AAA (ATPase associated with a variety of cellular activities) ATPase Vps4 and its co-factor Vta1p/LIP5 function in membrane remodeling events that accompany cytokinesis, multivesicular body biogenesis, and retrovirus budding, apparently by driving disassembly and recycling of membrane-associated ESCRT (endosomal sorting complex required for transport)-III complexes. Here, we present electron cryomicroscopy reconstructions of dodecameric yeast Vps4p complexes with and without their microtubule interacting and transport (MIT) N-terminal domains and Vta1p co-factors. The ATPase domains of Vps4p form a bowl-like structure composed of stacked hexameric rings. The two rings adopt dramatically different conformations, with the "upper" ring forming an open assembly that defines the sides of the bowl and the lower ring forming a closed assembly that forms the bottom of the bowl. The N-terminal MIT domains of the upper ring localize on the symmetry axis above the cavity of the bowl, and the binding of six extended Vta1p monomers causes additional density to appear both above and below the bowl. The structures suggest models in which Vps4p MIT and Vta1p domains engage ESCRT-III substrates above the bowl and help transfer them into the bowl to be pumped through the center of the dodecameric assembly.
Additional Information
Copyright © 2008 Elsevier Ltd. Received 10 August 2007; revised 1 January 2008; accepted 4 January 2008. Available online 12 January 2008. Edited by W. Baumeister. This work was supported in part by the National Institutes of Health through grant P50 GM082545 (awarded to W.I.S., C.P.H., and G.J.J.), the Beckman Institute at Caltech, and gifts to Caltech from the Ralph M. Parsons Foundation, the Agouron Institute, and the Gordon and Betty Moore Foundation. We thank E. Kubalek for sharing her cryo-EM structure of p97. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jmb.2008.01.009Attached Files
Accepted Version - nihms42854.pdf
Supplemental Material - YUZjmb08supp.pdf
Files
Name | Size | Download all |
---|---|---|
md5:8dddff19a7aa2b1f56cb9aac8959c883
|
2.0 MB | Preview Download |
md5:10025737c23a1e21edf409430ef1a9e6
|
1.7 MB | Preview Download |
Additional details
- PMCID
- PMC2279015
- Eprint ID
- 24670
- Resolver ID
- CaltechAUTHORS:20110803-162803480
- P50 GM082545
- NIH
- Caltech Beckman Institute
- Ralph M. Parsons Foundation
- Agouron Institute
- Gordon and Betty Moore Foundation
- Created
-
2011-08-04Created from EPrint's datestamp field
- Updated
-
2021-11-09Created from EPrint's last_modified field