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Title: Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture

Abstract

Dynamin-related proteins (DRPs) are large multidomain GTPases required for diverse membrane-remodeling events. DRPs self-assemble into helical structures, but how these structures are tailored to their cellular targets remains unclear. We demonstrate that the fungal DRP Vps1 primarily localizes to and functions at the endosomal compartment. We present crystal structures of a Vps1 GTPase–bundle signaling element (BSE) fusion in different nucleotide states to capture GTP hydrolysis intermediates and concomitant conformational changes. Using cryoEM, we determined the structure of full-length GMPPCP-bound Vps1. The Vps1 helix is more open and flexible than that of dynamin. This is due to further opening of the BSEs away from the GTPase domains. A novel interface between adjacent GTPase domains forms in Vps1 instead of the contacts between the BSE and adjacent stalks and GTPase domains as seen in dynamin. Disruption of this interface abolishes Vps1 function in vivo. Hence, Vps1 exhibits a unique helical architecture, highlighting structural flexibilities of DRP self-assembly.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1];  [1]; ORCiD logo [3]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [1]
  1. Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
  2. Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
  3. Department of Molecular Medicine, Cornell University, Ithaca, NY
  4. Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK, Electron Bio-Imaging Centre, Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1463214
Grant/Contract Number:  
AC02-06CH11357; W-31-109-Eng-38
Resource Type:
Published Article
Journal Name:
Journal of Cell Biology
Additional Journal Information:
Journal Name: Journal of Cell Biology Journal Volume: 217 Journal Issue: 10; Journal ID: ISSN 0021-9525
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
English

Citation Formats

Varlakhanova, Natalia V., Alvarez, Frances J. D., Brady, Tyler M., Tornabene, Bryan A., Hosford, Christopher J., Chappie, Joshua S., Zhang, Peijun, and Ford, Marijn G. J. Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture. United States: N. p., 2018. Web. doi:10.1083/jcb.201712021.
Varlakhanova, Natalia V., Alvarez, Frances J. D., Brady, Tyler M., Tornabene, Bryan A., Hosford, Christopher J., Chappie, Joshua S., Zhang, Peijun, & Ford, Marijn G. J. Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture. United States. doi:10.1083/jcb.201712021.
Varlakhanova, Natalia V., Alvarez, Frances J. D., Brady, Tyler M., Tornabene, Bryan A., Hosford, Christopher J., Chappie, Joshua S., Zhang, Peijun, and Ford, Marijn G. J. Tue . "Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture". United States. doi:10.1083/jcb.201712021.
@article{osti_1463214,
title = {Structures of the fungal dynamin-related protein Vps1 reveal a unique, open helical architecture},
author = {Varlakhanova, Natalia V. and Alvarez, Frances J. D. and Brady, Tyler M. and Tornabene, Bryan A. and Hosford, Christopher J. and Chappie, Joshua S. and Zhang, Peijun and Ford, Marijn G. J.},
abstractNote = {Dynamin-related proteins (DRPs) are large multidomain GTPases required for diverse membrane-remodeling events. DRPs self-assemble into helical structures, but how these structures are tailored to their cellular targets remains unclear. We demonstrate that the fungal DRP Vps1 primarily localizes to and functions at the endosomal compartment. We present crystal structures of a Vps1 GTPase–bundle signaling element (BSE) fusion in different nucleotide states to capture GTP hydrolysis intermediates and concomitant conformational changes. Using cryoEM, we determined the structure of full-length GMPPCP-bound Vps1. The Vps1 helix is more open and flexible than that of dynamin. This is due to further opening of the BSEs away from the GTPase domains. A novel interface between adjacent GTPase domains forms in Vps1 instead of the contacts between the BSE and adjacent stalks and GTPase domains as seen in dynamin. Disruption of this interface abolishes Vps1 function in vivo. Hence, Vps1 exhibits a unique helical architecture, highlighting structural flexibilities of DRP self-assembly.},
doi = {10.1083/jcb.201712021},
journal = {Journal of Cell Biology},
number = 10,
volume = 217,
place = {United States},
year = {2018},
month = {8}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1083/jcb.201712021

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Cited by: 2 works
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