Cryo-EM Structure of the Exocyst Complex

The exocyst is an evolutionarily conserved octameric protein complex that mediates the tethering of post-Golgi secretory vesicles to the plasma membrane during exocytosis and is implicated in many cellular processes such as cell polarization, cytokinesis, ciliogenesis and tumor invasion. Using cryo-EM and chemical cross-linking MS (CXMS), we solved the structure of the Saccharomyces cerevisiae exocyst complex at an average resolution of 4.4 Å. Our model revealed the architecture of the exocyst and led to the identification of the helical bundles that mediate the assembly of the complex at its core. Sequence analysis suggests that these regions are evolutionarily conserved across eukaryotic systems. Additional cell biological data suggest a mechanism for exocyst assembly that leads to vesicle tethering at the plasma membrane. The structure of the fully assembled yeast exocyst complex, which mediates the tethering of secretory vesicles to the plasma membrane during exocytosis, provides new insights to hierarchical complex assembly and the mechanism of vesicle tethering.

• Publication year

  2017

• Venue

  Nature Structural & Molecular Biology

• Publication date

  2017-12-15

• Fields of study

  Biology, Medicine, Materials Science, Chemistry

• Identifiers
  DOI 10.1038/s41594-017-0016-2PMID 29335562PMCID 5971111
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy

  2017cited by this paper
• Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2

  2017cited by this paper
• Crystal structure of Sec10, a subunit of the exocyst complex

  2017cited by this paper
• The In Vivo Architecture of the Exocyst Provides Structural Basis for Exocytosis.

  2017cited by this paper
• Sec3 promotes the initial binary t-SNARE complex assembly and membrane fusion

  2017cited by this paper
• An endosomal tether undergoes an entropic collapse to bring vesicles together

  2016cited by this paper
• Oncogenic BRAF-Mediated Melanoma Cell Invasion.

  2016cited by this paper
• An algorithm for estimation and correction of anisotropic magnification distortion of cryo-EM images without need of pre-calibration.

  2016cited by this paper
• Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers.

  2016cited by this paper
• Modeling Protein Excited-state Structures from “Over-length” Chemical Cross-links*

  2016cited by this paper
• CATCHR and HOPS-CORVET tethering complexes share a similar architecture

  2016cited by this paper
• The Phyre2 web portal for protein modeling, prediction and analysis

  2015cited by this paper
• Automatic estimation and correction of anisotropic magnification distortion in electron microscopes.

  2015cited by this paper
• Subunit connectivity, assembly determinants and architecture of the yeast exocyst complex

  2015cited by this paper
• Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

  2015cited by this paper
• Asynchronous data acquisition and on-the-fly analysis of dose fractionated cryoEM images by UCSFImage.

  2015cited by this paper
• The Exocyst at a Glance

  2015cited by this paper
• Molecular Architecture of the 40SeIF1eIF3 Translation Initiation Complex.

  2014cited by this paper
• The role of Sec3p in secretory vesicle targeting and exocyst complex assembly

  2014cited by this paper
• Beam-induced motion correction for sub-megadalton cryo-EM particles

  2014cited by this paper
• Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

  2014cited by this paper
• SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information

  2014cited by this paper
• The Local Resolution of Cryo-EM Density Maps

  2013cited by this paper
• Electron counting and beam-induced motion correction enable near atomic resolution single particle cryoEM

  2013cited by this paper
• Mitotic phosphorylation of Exo84 disrupts exocyst assembly and arrests cell growth

  2013cited by this paper
• RELION: Implementation of a Bayesian approach to cryo-EM structure determination

  2012cited by this paper
• Prevention of overfitting in cryo-EM structure determination

  2012cited by this paper
• Exorcising the Exocyst Complex

  2012cited by this paper
• Structural Probing of a Protein Phosphatase 2A Network by Chemical Cross-Linking and Mass Spectrometry

  2012cited by this paper
• ERK1/2 regulate exocytosis through direct phosphorylation of the exocyst component Exo70.

  2012cited by this paper
• Identification of cross-linked peptides from complex samples

  2012cited by this paper
• Structures and mechanisms of vesicle coat components and multisubunit tethering complexes.

  2012cited by this paper
• Single particle electron microscopy reconstruction of the exosome complex using the random conical tilt method.

  2011cited by this paper
• Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3*

  2010cited by this paper
• Multisubunit tethering complexes and their role in membrane fusion.

  2010cited by this paper
• Molecular organization of the COG vesicle tethering complex

  2010cited by this paper
• Tethering factors as organizers of intracellular vesicular traffic.

  2010cited by this paper
• Structural basis for the Rho- and phosphoinositide-dependent localization of the exocyst subunit Sec3

  2010cited by this paper
• Conservation of Helical Bundle Structure between the Exocyst Subunits

  2009cited by this paper
• MolProbity: all-atom structure validation for macromolecular crystallography

  2009cited by this paper
• The exocyst complex in polarized exocytosis.

  2009cited by this paper
• Membrane association and functional regulation of Sec3 by phospholipids and Cdc42

  2008cited by this paper
• SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs

  2008cited by this paper
• Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane

  2007cited by this paper
• EMAN2: an extensible image processing suite for electron microscopy.

  2007cited by this paper
• Phosphatidylinositol 4,5-bisphosphate mediates the targeting of the exocyst to the plasma membrane for exocytosis in mammalian cells.

  2007cited by this paper
• The crystal structure of mouse Exo70 reveals unique features of the mammalian exocyst.

  2007cited by this paper
• The exocyst defrocked, a framework of rods revealed

  2006cited by this paper
• The structure of the exocyst subunit Sec6p defines a conserved architecture with diverse roles

  2006cited by this paper
• Role of tethering factors in secretory membrane traffic.

  2006cited by this paper
• Sec15 interacts with Rab11 via a novel domain and affects Rab11 localization in vivo

  2005cited by this paper
• Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase

  2005cited by this paper
• Sec 15 interacts with Rab 11 via a novel domain and affects Rab 11 localization in vivo

  2005cited by this paper
• The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif

  2005cited by this paper
• Crystal structure of the S.cerevisiae exocyst component Exo70p.

  2005cited by this paper
• Coot: model-building tools for molecular graphics.

  2004cited by this paper
• Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p

  2004cited by this paper
• UCSF Chimera—A visualization system for exploratory research and analysis

  2004cited by this paper
• Ral GTPases Regulate Exocyst Assembly through Dual Subunit Interactions*

  2003cited by this paper
• Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex

  2003cited by this paper
• Accurate determination of local defocus and specimen tilt in electron microscopy.

  2003cited by this paper
• Exocytosis: the many masters of the exocyst.

  2002cited by this paper
• Ras family therapy: Rab, Rho and Ral talk to the exocyst.

  2002cited by this paper
• Vesicle tethering complexes in membrane traffic.

  2002cited by this paper
• The exocyst complex binds the small GTPase RalA to mediate filopodia formation

  2002cited by this paper
• The exocyst is a Ral effector complex

  2002cited by this paper
• Spatial regulation of the exocyst complex by Rho1 GTPase

  2001cited by this paper
• The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic.

  2001cited by this paper
• Protein complexes in transport vesicle targeting.

  2000cited by this paper
• Correspondence e-mail:

  2000cited by this paper
• Targeting vesicles to specific sites on the plasma membrane: the role of the sec6/8 complex.

  1999cited by this paper
• Transport-vesicle targeting: tethers before SNAREs

  1999cited by this paper
• Situs: A package for docking crystal structures into low-resolution maps from electron microscopy.

  1999cited by this paper
• Sec3p is a spatial landmark for polarized secretion in budding yeast.

  1998cited by this paper
• Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution

  1998cited by this paper
• The Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae.

  1996cited by this paper
• Sec6, Sec8, and Sec15 are components of a multisubunit complex which localizes to small bud tips in Saccharomyces cerevisiae

  1995cited by this paper
• Electronic Reprint Biological Crystallography Phenix : a Comprehensive Python-based System for Macromolecular Structure Solution

  year unknowncited by this paper

• Continuum architecture dynamics of vesicle tethering in exocytosis.

  2026cites this paper
• Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense

  2026cites this paper
• Molecular choreography of vesicle trafficking: Exocyst-SNARE interplay in plant defense.

  2026cites this paper
• Collective Noise Filtering in Complex Networks

  2026cites this paper
• Evolutionary analysis of the exocyst complex in streptophytes links early EXO70 diversification with dominance over SEC3 in membrane targeting

  2026cites this paper
• NUT1-Exo70A1 Regulates Xylem Vessel Development and Influences Water Use Efficiency in Maize.

  2026cites this paper
• COG Complex in Golgi Trafficking and Glycosylation.

  2026cites this paper
• ExoFILT: Transfer learning for robust and accelerated analysis of exocytosis single-particle tracking data

  2026cites this paper
• Structural extension of the human exocyst is enabled by a minimal interface.

  2026cites this paper
• Structural insights into traffic through the Golgi complex.

  2025cites this paper
• Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

  2025influential citation
• The autophagy-specific exocyst subcomplex contributes to phagophore assembly site integrity by promoting phagophore expansion.

  2025cites this paper
• Sec10 suppresses antiviral innate immune response by facilitating STUB1-mediated STAT1 degradation

  2025cites this paper
• The Ral small GTPase is an essential regulator of Exocyst complex function in secretion

  2025cites this paper
• The C-terminal domain of SEC-10 is fundamental for exocyst function, apical organization, and cell morphogenesis in Neurospora crassa.

  2025cites this paper
• The exocyst in ciliogenesis

  2025cites this paper
• A large-scale curated and filterable dataset for cryo-EM foundation model pre-training

  2025cites this paper
• Unveiling EXOC4/SEC8: a key player in enhancing antiviral immunity by inhibiting the FBXL19-STING1-SQSTM1 signaling axis

  2025cites this paper
• A tale of Rabs and the exocyst complex in ciliary trafficking and biogenesis

  2025cites this paper
• The role of Exo70s in plant defense against pathogens and insect pests and their application for crop breeding

  2025cites this paper
• Preassembly and independent trafficking of the exocyst complex in Arabidopsis

  2025cites this paper
• OsSEC3A, a key exocyst subunit, is required for the emergence of crown root in rice

  2025cites this paper
• Electrostatic changes enabled the diversification of an exocyst subunit via protein complex escape

  2025cites this paper
• Subcellular spatial regulation of immunity-induced phosphorylation of RIN4 links PAMP-triggered immunity to Exo70B1

  2024cites this paper
• Structural extension of the human exocyst is enabled by a minimal interface

  2024cites this paper
• The exocyst in context

  2024influential citation
• Exocyst stimulates multiple steps of exocytic SNARE complex assembly and vesicle fusion

  2024cites this paper
• Emerging Roles of Exocyst Complex in Fungi: A Review

  2024cites this paper
• TGM1/3-mediated transamidation of Exo70 promotes tumor metastasis upon LKB1 inactivation.

  2024cites this paper
• Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

  2024cites this paper
• A chemical genetic screen with the EXO70 inhibitor Endosidin2 uncovers potential modulators of exocytosis in Arabidopsis

  2024cites this paper
• Tagging of Exo70 at the N-terminus compromises its assembly with the exocyst complex and changes its spatiotemporal behavior at the plasma membrane

  2024cites this paper
• Single‐Molecule Electrical Profiling of Peptides and Proteins

  2024cites this paper
• Use of Protein interactions from Imaging Complexes after Translocation (PICT) to characterise in situ the spatial configuration of proteins interacting with the exocyst

  2024cites this paper
• Exo84c-regulated degradation is involved in the normal self-incompatible response in Brassicaceae.

  2024cites this paper
• Deletion of Exoc7, but not Exoc3, in male germ cells causes severe spermatogenesis failure with spermatocyte aggregation in mice

  2024cites this paper
• Structure of a Membrane Tethering Complex Incorporating Multiple SNAREs

  2023influential citation
• Exploitation of the host exocyst complex by bacterial pathogens

  2023cites this paper
• The exocyst complex is an evolutionary battleground in plant-microbe interactions.

  2023cites this paper
• A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion

  2023cites this paper
• Exo84c interacts with VAP27 to regulate exocytotic compartment degradation and stigma senescence

  2023cites this paper
• Highly efficient overexpression and purification of multisubunit tethering complexes in Saccharomyces cerevisiae.

  2023cites this paper
• Asymmetric tethering by exocyst in vitro requires a Rab GTPase, an R-SNARE and a Sac1-sensitive phosphoinositide lipid

  2023cites this paper
• Genome‐wide association study of Helicobacter pylori serological status in Latin American children

  2023cites this paper
• The machinery of vesicle fusion.

  2023cites this paper
• Lessons from the deep: mechanisms behind diversification of eukaryotic protein complexes

  2023cites this paper
• The Exocyst Complex is Required for the Trafficking and Delivery of KCa3.1 to the Basolateral Membrane of Polarized Epithelia.

  2023cites this paper
• The exocyst complex in neurological disorders

  2023cites this paper
• SEC. 1A and SEC. 6 synergistically regulate pollen tube polar growth.

  2023cites this paper
• Allosteric regulation of exocyst: Discrete activation of tethering by two spatial signals

  2023cites this paper
• Comparative analysis of chemical cross-linking mass spectrometry data indicates that protein STY residues rarely react with N-hydroxysuccinimide ester cross-linkers

  2023cites this paper
• Modeling the Cryo-EM Structure of the Exocyst Complex.

  2023cites this paper
• The functional and structural characterization of Xanthomonas campestris pv. campestris core effector XopP revealed a new kinase activity.

  2023cites this paper
• Binding of a blast fungus Zinc-finger fold effector to a hydrophobic pocket in the host exocyst subunit Exo70 modulates immune recognition in rice

  2022cites this paper
• A blast fungus zinc-finger fold effector binds to a hydrophobic pocket in host Exo70 proteins to modulate immune recognition in rice

  2022cites this paper
• Better Cryo-EM Specimen Preparation: How to Deal with the Air-Water Interface?

  2022cites this paper
• Cancer cells resist antibody-mediated destruction by neutrophils through activation of the exocyst complex

  2022cites this paper
• The host exocyst complex is targeted by a conserved bacterial type-III effector that promotes virulence.

  2022cites this paper
• A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder

  2022influential citation
• The functional and structural characterization of Xanthomonas campestris pv. campestris core effector XopP revealed a new kinase activity

  2022cites this paper
• High-resolution secretory timeline from vesicle formation at the Golgi to fusion at the plasma membrane in S. cerevisiae

  2022cites this paper
• Structural basis for assembly of TRAPPII complex and specific activation of GTPase Ypt31/32

  2022cites this paper
• Exocyst stimulates each step of exocytic SNARE complex assembly and vesicle fusion

  2022cites this paper
• Vesicle transport: Exocyst follows PIP2 to tether membranes.

  2022cites this paper
• Grab regulates transferrin receptor recycling and iron uptake in developing erythroblasts.

  2022cites this paper
• Determine the Function of the Exocyst in Vesicle Tethering by Ectopic Targeting.

  2022cites this paper
• An isoform-specific function of Cdc42 in regulating mammalian Exo70 during axon formation

  2022influential citation
• Computed structures of core eukaryotic protein complexes

  2021cites this paper
• Secretory Vesicles Targeted to Plasma Membrane During Pollen Germination and Tube Growth

  2021cites this paper
• Loss of the exocyst complex component EXOC3 promotes hemostasis and accelerates arterial thrombosis.

  2021cites this paper
• Insights on autophagosome–lysosome tethering from structural and biochemical characterization of human autophagy factor EPG5

  2021cites this paper
• The fungal RABOME: RAB GTPases acting in the endocytic and exocytic pathways of Aspergillus nidulans (with excursions to other filamentous fungi)

  2021cites this paper
• Sec3 exocyst component knockdown inhibits axonal formation and cortical neuronal migration during brain cortex development

  2021cites this paper
• Homology and Modular Evolution of CATCHR at the Origin of the Eukaryotic Endomembrane System

  2021cites this paper
• Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling

  2021cites this paper
• An exocyst component, Sec5, is essential for ascospore formation in Bipolaris maydis

  2021cites this paper
• The exocyst complex regulates C. elegans germline stem cell proliferation by controlling membrane Notch levels.

  2021cites this paper
• Plasma membrane phospholipid signature recruits the plant exocyst complex via the EXO70A1 subunit

  2021cites this paper
• Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases

  2021cites this paper
• RASSF8-mediated transport of Echinoid via the exocyst promotes Drosophila wing elongation and epithelial ordering

  2021cites this paper
• dRASSF8 interacts with Sec15 to regulate Adherens Junctions Stability

  2021cites this paper
• The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium

  2021influential citation
• Structures of core eukaryotic protein complexes

  2021cites this paper
• Shigella flexneri subverts host polarized exocytosis to enhance cell‐to‐cell spread

  2021cites this paper
• A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion

  2021cites this paper
• Exocyst complex mediates recycling of internal cilia.

  2021cites this paper
• Endocytosis mediated by an atypical CUBAM complex modulates slit diaphragm dynamics in nephrocytes

  2021cites this paper
• Cross-Linking Mass Spectrometry for Investigating Protein Conformations and Protein-Protein Interactions─A Method for All Seasons.

  2021cites this paper
• Phosphoinositides containing stearic acid are required for interaction between Rho GTPases and the exocyst to control the late steps of polarized exocytosis

  2021cites this paper
• A lineage-specific Exo70 is required for receptor kinase–mediated immunity in barley

  2021influential citation
• Advances in Understanding the Structure and Function of the Exocyst Complex

  2021cites this paper
• Phosphoinositides containing stearic acid are required for interaction between Rho GTPases and the exocyst to control the late steps of polarised exocytosis

  2021cites this paper
• ULK1 phosphorylates Exo70 to suppress breast cancer metastasis

  2020cites this paper
• Exocyst structural changes associated with activation of tethering downstream of Rho/Cdc42 GTPases

  2020cites this paper
• Exocyst subunit Exo70B2 is linked to immune signaling and autophagy.

  2020cites this paper
• Synergy among Exocyst and SNARE Interactions Identifies a Functional Hierarchy in Secretion during Vegetative Growth.

  2020cites this paper
• The host exocyst complex is targeted by a conserved bacterial type III effector protein that promotes virulence

  2020cites this paper
• Glutamatergic Receptor Trafficking and Delivery: Role of the Exocyst Complex

  2020cites this paper
• Recent Advances in Single-Particle Electron Microscopic Analysis of Autophagy Degradation Machinery

  2020cites this paper
• The N-terminus of Sec3 is required for cell wall integrity in yeast.

  2020cites this paper