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:
- 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. https://doi.org/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. https://doi.org/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 = {Tue Aug 07 00:00:00 EDT 2018},
month = {Tue Aug 07 00:00:00 EDT 2018}
}
https://doi.org/10.1083/jcb.201712021
Web of Science
Works referenced in this record:
Essential Role of the Dynamin Pleckstrin Homology Domain in Receptor-Mediated Endocytosis
journal, February 1999
- Achiriloaie, Mircea; Barylko, Barbara; Albanesi, Joseph P.
- Molecular and Cellular Biology, Vol. 19, Issue 2
Structural basis for mechanochemical role of Arabidopsis thaliana dynamin-related protein in membrane fission
journal, January 2011
- Yan, Liming; Ma, Yuanyuan; Sun, Yuna
- Journal of Molecular Cell Biology, Vol. 3, Issue 6
A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast
journal, March 1995
- Vida, T. A.
- The Journal of Cell Biology, Vol. 128, Issue 5
Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae
journal, October 2006
- Kuravi, K.
- Journal of Cell Science, Vol. 119, Issue 19
Structural basis for conformational switching and GTP loading of the large G protein atlastin
journal, January 2013
- Byrnes, Laura J.; Singh, Avtar; Szeto, Kylan
- The EMBO Journal, Vol. 32, Issue 3
G domain dimerization controls dynamin's assembly-stimulated GTPase activity
journal, April 2010
- Chappie, Joshua S.; Acharya, Sharmistha; Leonard, Marilyn
- Nature, Vol. 465, Issue 7297
Insight into Structure and Assembly of the Nuclear Pore Complex by Utilizing the Genome of a Eukaryotic Thermophile
journal, July 2011
- Amlacher, Stefan; Sarges, Phillip; Flemming, Dirk
- Cell, Vol. 146, Issue 2
Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients
journal, August 2010
- Kenniston, Jon A.; Lemmon, Mark A.
- The EMBO Journal, Vol. 29, Issue 18
Structure of Myxovirus Resistance Protein A Reveals Intra- and Intermolecular Domain Interactions Required for the Antiviral Function
journal, October 2011
- Gao, Song; von der Malsburg, Alexander; Dick, Alexej
- Immunity, Vol. 35, Issue 4
Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012
- Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
A Pseudoatomic Model of the Dynamin Polymer Identifies a Hydrolysis-Dependent Powerstroke
journal, September 2011
- Chappie, Joshua S.; Mears, Jason A.; Fang, Shunming
- Cell, Vol. 147, Issue 1
Fission of SNX-BAR–coated endosomal retrograde transport carriers is promoted by the dynamin-related protein Vps1
journal, February 2014
- Chi, Richard J.; Liu, Jingxuan; West, Matthew
- The Journal of Cell Biology, Vol. 204, Issue 5
A bacterial dynamin-like protein
journal, November 2006
- Low, Harry H.; Löwe, Jan
- Nature, Vol. 444, Issue 7120
Protein sorting in yeast: Mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway
journal, December 1986
- Rothman, Joel H.; Stevens, Tom H.
- Cell, Vol. 47, Issue 6
Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein
journal, April 2013
- Fröhlich, Chris; Grabiger, Stefan; Schwefel, David
- The EMBO Journal, Vol. 32, Issue 9
Dynamin, a membrane-remodelling GTPase
journal, January 2012
- Ferguson, Shawn M.; De Camilli, Pietro
- Nature Reviews Molecular Cell Biology, Vol. 13, Issue 2
The iterative helical real space reconstruction method: Surmounting the problems posed by real polymers
journal, January 2007
- Egelman, Edward H.
- Journal of Structural Biology, Vol. 157, Issue 1
Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells
journal, September 2000
- Gillooly, D. J.
- The EMBO Journal, Vol. 19, Issue 17
Structures of human mitofusin 1 provide insight into mitochondrial tethering
journal, December 2016
- Qi, Yuanbo; Yan, Liming; Yu, Caiting
- The Journal of Cell Biology, Vol. 215, Issue 5
A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting
journal, June 1990
- Rothman, Joel H.; Raymond, Christopher K.; Gilbert, Teresa
- Cell, Vol. 61, Issue 6
CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction
journal, September 2017
- Alvarez, Frances J. D.; He, Shaoda; Perilla, Juan R.
- Science Advances, Vol. 3, Issue 9
CTFFIND4: Fast and accurate defocus estimation from electron micrographs
journal, November 2015
- Rohou, Alexis; Grigorieff, Nikolaus
- Journal of Structural Biology, Vol. 192, Issue 2
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
journal, February 2017
- Zheng, Shawn Q.; Palovcak, Eugene; Armache, Jean-Paul
- Nature Methods, Vol. 14, Issue 4
Scaling and assessment of data quality
journal, December 2005
- Evans, Philip
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1, p. 72-82
A Dynamin Mutant Defines a Superconstricted Prefission State
journal, August 2014
- Sundborger, Anna C.; Fang, Shunming; Heymann, Jürgen A.
- Cell Reports, Vol. 8, Issue 3
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
Yeast Dynamin Vps1 and Amphiphysin Rvs167 Function Together During Endocytosis: Vps1 and Rvs167 Function Together in Endocytosis
journal, December 2011
- Smaczynska-de Rooij, Iwona I.; Allwood, Ellen G.; Mishra, Ritu
- Traffic, Vol. 13, Issue 2
Structure of a Bacterial Dynamin-like Protein Lipid Tube Provides a Mechanism For Assembly and Membrane Curving
journal, December 2009
- Low, Harry H.; Sachse, Carsten; Amos, Linda A.
- Cell, Vol. 139, Issue 7
UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004
- Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
- Journal of Computational Chemistry, Vol. 25, Issue 13
Induction of mutant dynamin specifically blocks endocytic coated vesicle formation
journal, November 1994
- Damke, H.
- The Journal of Cell Biology, Vol. 127, Issue 4
Mutual Control of Membrane Fission and Fusion Proteins
journal, November 2004
- Peters, Christopher; Baars, Tonie L.; Bühler, Susanne
- Cell, Vol. 119, Issue 5
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion
journal, January 2017
- Cao, Yu-Lu; Meng, Shuxia; Chen, Yang
- Nature, Vol. 542, Issue 7641
The dynamin superfamily: universal membrane tubulation and fission molecules?
journal, February 2004
- Praefcke, Gerrit J. K.; McMahon, Harvey T.
- Nature Reviews Molecular Cell Biology, Vol. 5, Issue 2
The VPS4 gene is involved in protein transport out of a yeast pre-vacuolar endosome-like compartment
journal, July 1997
- Finken-Eigen, Marion; Röhricht, Ralf A.; Köhrer, K.
- Current Genetics, Vol. 31, Issue 6
Yeast dynamin associates with the GARP tethering complex for endosome-to-Golgi traffic
journal, September 2017
- Saimani, Uma; Smothers, Jared; McDermott, Hyoeun
- European Journal of Cell Biology, Vol. 96, Issue 6
SPRING – An image processing package for single-particle based helical reconstruction from electron cryomicrographs
journal, January 2014
- Desfosses, Ambroise; Ciuffa, Rodolfo; Gutsche, Irina
- Journal of Structural Biology, Vol. 185, Issue 1
Measuring piecemeal microautophagy of the nucleus in Saccharomyces cerevisiae
journal, January 2009
- Millen, Jonathan I.; Krick, Roswitha; Prick, Tanja
- Autophagy, Vol. 5, Issue 1
Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes
journal, February 2011
- Bian, X.; Klemm, R. W.; Liu, T. Y.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 10
Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p
journal, April 1997
- Babst, M.
- The EMBO Journal, Vol. 16, Issue 8
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM
journal, March 2011
- Battye, T. Geoff G.; Kontogiannis, Luke; Johnson, Owen
- Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4
Vps1, a recycling factor for the traffic from early endosome to the late Golgi
journal, December 2013
- Lukehart, Joshua; Highfill, Chad; Kim, Kyoungtae
- Biochemistry and Cell Biology, Vol. 91, Issue 6
Dnm1 forms spirals that are structurally tailored to fit mitochondria
journal, September 2005
- Ingerman, Elena; Perkins, Edward M.; Marino, Michael
- The Journal of Cell Biology, Vol. 170, Issue 7
Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles
journal, December 2004
- Fratti, Rutilio A.; Jun, Youngsoo; Merz, Alexey J.
- The Journal of Cell Biology, Vol. 167, Issue 6
EMAN2: An extensible image processing suite for electron microscopy
journal, January 2007
- Tang, Guang; Peng, Liwei; Baldwin, Philip R.
- Journal of Structural Biology, Vol. 157, Issue 1
Reverse-topology membrane scission by the ESCRT proteins
journal, October 2016
- Schöneberg, Johannes; Lee, Il-Hyung; Iwasa, Janet H.
- Nature Reviews Molecular Cell Biology, Vol. 18, Issue 1
Building a fission machine - structural insights into dynamin assembly and activation
journal, June 2013
- Chappie, J. S.; Dyda, F.
- Journal of Cell Science, Vol. 126, Issue 13
Membrane fission by dynamin: what we know and what we need to know
journal, September 2016
- Antonny, Bruno; Burd, Christopher; De Camilli, Pietro
- The EMBO Journal, Vol. 35, Issue 21
Deciphering key features in protein structures with the new ENDscript server
journal, April 2014
- Robert, Xavier; Gouet, Patrice
- Nucleic Acids Research, Vol. 42, Issue W1
Crystal structure of the dynamin tetramer
journal, August 2015
- Reubold, Thomas F.; Faelber, Katja; Plattner, Nuria
- Nature, Vol. 525, Issue 7569
Phosphatidylinositol(3)-Phosphate Signaling Mediated by Specific Binding to RING FYVE Domains
journal, July 1998
- Burd, Christopher G.; Emr, Scott D.
- Molecular Cell, Vol. 2, Issue 1
Features and development of Coot
journal, March 2010
- Emsley, P.; Lohkamp, B.; Scott, W. G.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state
journal, January 2016
- Anand, Roopsee; Eschenburg, Susanne; Reubold, Thomas F.
- Biochemical and Biophysical Research Communications, Vol. 469, Issue 1
Fiji: an open-source platform for biological-image analysis
journal, June 2012
- Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
- Nature Methods, Vol. 9, Issue 7
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Cryo-EM Studies of Drp1 Reveal Cardiolipin Interactions that Activate the Helical Oligomer
journal, September 2017
- Francy, Christopher A.; Clinton, Ryan W.; Fröhlich, Chris
- Scientific Reports, Vol. 7, Issue 1
Vps1 in the late endosome-to-vacuole traffic
journal, January 2013
- Hayden, Jacob; Williams, Michelle; Granich, Ann
- Journal of Biosciences, Vol. 38, Issue 1
Helical reconstruction in RELION
journal, June 2017
- He, Shaoda; Scheres, Sjors H. W.
- Journal of Structural Biology, Vol. 198, Issue 3
Specific Retrieval of the Exocytic SNARE Snc1p from Early Yeast Endosomes
journal, January 2000
- Lewis, Michael J.; Nichols, Benjamin J.; Prescianotto-Baschong, Cristina
- Molecular Biology of the Cell, Vol. 11, Issue 1
Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants.
journal, December 1992
- Raymond, C. K.; Howald-Stevenson, I.; Vater, C. A.
- Molecular Biology of the Cell, Vol. 3, Issue 12
Crystal structure of nucleotide-free dynamin
journal, September 2011
- Faelber, Katja; Posor, York; Gao, Song
- Nature, Vol. 477, Issue 7366
MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004
- Edgar, R. C.
- Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
The crystal structure of dynamin
journal, September 2011
- Ford, Marijn G. J.; Jenni, Simon; Nunnari, Jodi
- Nature, Vol. 477, Issue 7366
Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring
journal, May 1999
- Stowell, Michael H. B.; Marks, Bruno; Wigge, Patrick
- Nature Cell Biology, Vol. 1, Issue 1
Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles
journal, December 2014
- Arlt, H.; Reggiori, F.; Ungermann, C.
- Journal of Cell Science, Vol. 128, Issue 4
The Machines that Divide and Fuse Mitochondria
journal, June 2007
- Hoppins, Suzanne; Lackner, Laura; Nunnari, Jodi
- Annual Review of Biochemistry, Vol. 76, Issue 1
Dynamin GTPase is stimulated by crosslinking through the C-terminal proline-rich domain.
journal, April 1995
- Warnock, D. E.; Terlecky, L. J.; Schmid, S. L.
- The EMBO Journal, Vol. 14, Issue 7
Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A
journal, January 2011
- Byrnes, L. J.; Sondermann, H.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 6
Early stages in the yeast secretory pathway are required for transport of carboxypeptidase Y to the vacuole
journal, September 1982
- Stevens, Tom; Esmon, Brent; Schekman, Randy
- Cell, Vol. 30, Issue 2
SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs
journal, October 2008
- Shaikh, Tanvir R.; Gao, Haixiao; Baxter, William T.
- Nature Protocols, Vol. 3, Issue 12
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
The VPS1 protein, a homolog of dynamin required for vacuolar protein sorting in Saccharomyces cerevisiae, is a GTPase with two functionally separable domains
journal, November 1992
- Vater, C. A.
- The Journal of Cell Biology, Vol. 119, Issue 4
A role for the dynamin-like protein Vps1 during endocytosis in yeast
journal, September 2010
- Rooij, I. I. S. -d.; Allwood, E. G.; Aghamohammadzadeh, S.
- Journal of Cell Science, Vol. 123, Issue 20
Structural basis of oligomerization in the stalk region of dynamin-like MxA
journal, April 2010
- Gao, Song; von der Malsburg, Alexander; Paeschke, Susann
- Nature, Vol. 465, Issue 7297