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

Journal Article · · Journal of Cell Biology
 [1];  [2];  [1];  [1];  [3];  [3];  [4];  [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

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.

Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
NIH
OSTI ID:
1479024
Journal Information:
Journal of Cell Biology, Journal Name: Journal of Cell Biology Journal Issue: 10 Vol. 217; ISSN 0021-9525
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
ENGLISH

References (78)

Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells journal September 2000
Reverse-topology membrane scission by the ESCRT proteins journal October 2016
Helical reconstruction in RELION journal June 2017
Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles journal December 2004
Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring journal May 1999
Vps1, a recycling factor for the traffic from early endosome to the late Golgi journal December 2013
Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants. journal December 1992
Features and development of Coot journal March 2010
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
Essential Role of the Dynamin Pleckstrin Homology Domain in Receptor-Mediated Endocytosis journal February 1999
Membrane fission by dynamin: what we know and what we need to know journal September 2016
G domain dimerization controls dynamin's assembly-stimulated GTPase activity journal April 2010
Assembly of the AAA ATPase Vps4 on ESCRT-III journal March 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Dynamin GTPase is stimulated by crosslinking through the C-terminal proline-rich domain. journal April 1995
Structural insights into oligomerization and mitochondrial remodelling of dynamin 1-like protein journal April 2013
EMAN2: An extensible image processing suite for electron microscopy journal January 2007
Scaling and assessment of data quality journal December 2005
Structural basis for mechanochemical role of Arabidopsis thaliana dynamin-related protein in membrane fission journal January 2011
Phaser crystallographic software journal July 2007
SPRING – An image processing package for single-particle based helical reconstruction from electron cryomicrographs journal January 2014
Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae journal October 2006
Dynamin, a membrane-remodelling GTPase journal January 2012
Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A journal January 2011
The CCP4 suite programs for protein crystallography journal September 1994
Mutual Control of Membrane Fission and Fusion Proteins journal November 2004
Cryo-EM Studies of Drp1 Reveal Cardiolipin Interactions that Activate the Helical Oligomer journal September 2017
The crystal structure of dynamin journal September 2011
Three new dominant drug resistance cassettes for gene disruption inSaccharomyces cerevisiae journal October 1999
Phosphatidylinositol(3)-Phosphate Signaling Mediated by Specific Binding to RING FYVE Domains journal July 1998
Structures of human mitofusin 1 provide insight into mitochondrial tethering journal December 2016
Structure of a Bacterial Dynamin-like Protein Lipid Tube Provides a Mechanism For Assembly and Membrane Curving journal December 2009
Yeast Dynamin Vps1 and Amphiphysin Rvs167 Function Together During Endocytosis: Vps1 and Rvs167 Function Together in Endocytosis journal December 2011
The Machines that Divide and Fuse Mitochondria journal June 2007
Structure of Myxovirus Resistance Protein A Reveals Intra- and Intermolecular Domain Interactions Required for the Antiviral Function journal October 2011
SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs journal October 2008
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion journal January 2017
Structural basis for conformational switching and GTP loading of the large G protein atlastin journal January 2013
The iterative helical real space reconstruction method: Surmounting the problems posed by real polymers journal January 2007
Retromer and the dynamin Vps1 cooperate in the retrieval of transmembrane proteins from vacuoles journal December 2014
Structural basis of oligomerization in the stalk region of dynamin-like MxA journal April 2010
Induction of mutant dynamin specifically blocks endocytic coated vesicle formation journal November 1994
CTFFIND4: Fast and accurate defocus estimation from electron micrographs journal November 2015
A Pseudoatomic Model of the Dynamin Polymer Identifies a Hydrolysis-Dependent Powerstroke journal September 2011
Yeast dynamin associates with the GARP tethering complex for endosome-to-Golgi traffic journal September 2017
Building a fission machine - structural insights into dynamin assembly and activation journal June 2013
Crystal structure of the dynamin tetramer journal August 2015
A bacterial dynamin-like protein journal November 2006
iMOSFLM : a new graphical interface for diffraction-image processing with MOSFLM journal March 2011
Early stages in the yeast secretory pathway are required for transport of carboxypeptidase Y to the vacuole journal September 1982
A Dynamin Mutant Defines a Superconstricted Prefission State journal August 2014
Dnm1 forms spirals that are structurally tailored to fit mitochondria journal September 2005
Towards automated crystallographic structure refinement with phenix.refine journal March 2012
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
Deciphering key features in protein structures with the new ENDscript server journal April 2014
Fission of SNX-BAR–coated endosomal retrograde transport carriers is promoted by the dynamin-related protein Vps1 journal February 2014
The VPS4 gene is involved in protein transport out of a yeast pre-vacuolar endosome-like compartment journal July 1997
MUSCLE: multiple sequence alignment with high accuracy and high throughput journal March 2004
A role for the dynamin-like protein Vps1 during endocytosis in yeast journal September 2010
Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes journal February 2011
Protein sorting in yeast: Mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway journal December 1986
Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients journal August 2010
Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae journal July 1998
Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state journal January 2016
Fiji: an open-source platform for biological-image analysis journal June 2012
Crystal structure of nucleotide-free dynamin journal September 2011
Insight into Structure and Assembly of the Nuclear Pore Complex by Utilizing the Genome of a Eukaryotic Thermophile journal July 2011
Membrane Insertion of the Pleckstrin Homology Domain Variable Loop 1 Is Critical for Dynamin-catalyzed Vesicle Scission journal November 2009
A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting journal June 1990
CryoEM structure of MxB reveals a novel oligomerization interface critical for HIV restriction journal September 2017
An Intramolecular Signaling Element that Modulates Dynamin Function In Vitro and In Vivo journal August 2009
Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p journal April 1997
Measuring piecemeal microautophagy of the nucleus in Saccharomyces cerevisiae journal January 2009
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy journal February 2017
Vps1 in the late endosome-to-vacuole traffic journal January 2013
Specific Retrieval of the Exocytic SNARE Snc1p from Early Yeast Endosomes journal January 2000
A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast journal March 1995
The dynamin superfamily: universal membrane tubulation and fission molecules? journal February 2004

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