+Open data
-Basic information
Entry | Database: PDB / ID: 7m0r | ||||||||||||||||||
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Title | Cryo-EM structure of the Sema3A/PlexinA4/Neuropilin 1 complex | ||||||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / plexin / semaphorin / neuropilin / signaling | ||||||||||||||||||
Function / homology | Function and homology information Neurophilin interactions with VEGF and VEGFR / neural crest cell migration involved in sympathetic nervous system development / glossopharyngeal nerve morphogenesis / chemorepulsion of branchiomotor axon / regulation of negative chemotaxis / vagus nerve morphogenesis / cell migration involved in coronary vasculogenesis / cranial nerve morphogenesis / trigeminal nerve morphogenesis / anterior commissure morphogenesis ...Neurophilin interactions with VEGF and VEGFR / neural crest cell migration involved in sympathetic nervous system development / glossopharyngeal nerve morphogenesis / chemorepulsion of branchiomotor axon / regulation of negative chemotaxis / vagus nerve morphogenesis / cell migration involved in coronary vasculogenesis / cranial nerve morphogenesis / trigeminal nerve morphogenesis / anterior commissure morphogenesis / Signal transduction by L1 / regulation of axon extension involved in axon guidance / postganglionic parasympathetic fiber development / facial nerve morphogenesis / sympathetic neuron axon guidance / CRMPs in Sema3A signaling / basal dendrite development / otic placode development / positive regulation of smooth muscle cell chemotaxis / protein localization to early endosome / Sema3A PAK dependent Axon repulsion / basal dendrite arborization / dichotomous subdivision of terminal units involved in salivary gland branching / retina vasculature morphogenesis in camera-type eye / regulation of vascular endothelial growth factor receptor signaling pathway / vestibulocochlear nerve structural organization / semaphorin receptor binding / dorsal root ganglion morphogenesis / ventral trunk neural crest cell migration / sympathetic neuron projection guidance / facioacoustic ganglion development / trigeminal ganglion development / epithelial cell migration / neurofilament / postsynapse organization / trigeminal nerve structural organization / sensory neuron axon guidance / facial nerve structural organization / gonadotrophin-releasing hormone neuronal migration to the hypothalamus / branchiomotor neuron axon guidance / renal artery morphogenesis / positive regulation of male gonad development / cerebellar climbing fiber to Purkinje cell synapse / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / maintenance of synapse structure / negative regulation of axon extension involved in axon guidance / axon extension involved in axon guidance / VEGF-activated neuropilin signaling pathway / synaptic target recognition / sympathetic neuron projection extension / blood vessel endothelial cell migration / negative regulation of epithelial cell migration / vascular endothelial growth factor binding / retina vasculature development in camera-type eye / endothelial cell chemotaxis / motor neuron migration / axonogenesis involved in innervation / sympathetic ganglion development / neural crest cell migration involved in autonomic nervous system development / positive regulation of axon extension involved in axon guidance / positive regulation of platelet-derived growth factor receptor signaling pathway / vascular endothelial growth factor receptor activity / negative regulation of axon extension / nerve development / semaphorin receptor complex / positive regulation of neuron migration / olfactory bulb development / angiogenesis involved in coronary vascular morphogenesis / neuropilin signaling pathway / sympathetic nervous system development / neuropilin binding / coronary artery morphogenesis / hepatocyte growth factor receptor signaling pathway / substrate-dependent cell migration, cell extension / outflow tract septum morphogenesis / chemorepellent activity / semaphorin receptor activity / commissural neuron axon guidance / negative regulation of cell adhesion / embryonic heart tube development / axon extension / positive regulation of vascular associated smooth muscle cell migration / motor neuron axon guidance / cell migration involved in sprouting angiogenesis / axonal fasciculation / regulation of Cdc42 protein signal transduction / sprouting angiogenesis / dendrite morphogenesis / neural crest cell migration / positive regulation of filopodium assembly / artery morphogenesis / negative chemotaxis / positive regulation of cell migration involved in sprouting angiogenesis / branching involved in blood vessel morphogenesis / positive regulation of axonogenesis / cellular response to hepatocyte growth factor stimulus / retinal ganglion cell axon guidance / positive chemotaxis / dendrite development / growth factor binding Similarity search - Function | ||||||||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.7 Å | ||||||||||||||||||
Authors | Lu, D. / Shang, G. / He, X. / Bai, X. / Zhang, X. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: Nat Commun / Year: 2021 Title: Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex. Authors: Defen Lu / Guijun Shang / Xiaojing He / Xiao-Chen Bai / Xuewu Zhang / Abstract: Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for ...Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture of and the molecular interactions in the Sema3/plexin/neuropilin complex are incompletely understood. Here we present the cryo-EM structure of a near intact extracellular region complex of Sema3A, PlexinA4 and Neuropilin 1 (Nrp1) at 3.7 Å resolution. The structure shows a large symmetric 2:2:2 assembly in which each subunit makes multiple interactions with others. The two PlexinA4 molecules in the complex do not interact directly, but their membrane proximal regions are close to each other and poised to promote the formation of the intracellular active dimer for signaling. The structure reveals a previously unknown interface between the a2b1b2 module in Nrp1 and the Sema domain of Sema3A. This interaction places the a2b1b2 module at the top of the complex, far away from the plasma membrane where the transmembrane regions of Nrp1 and PlexinA4 embed. As a result, the region following the a2b1b2 module in Nrp1 must span a large distance to allow the connection to the transmembrane region, suggesting an essential role for the long non-conserved linkers and the MAM domain in neuropilin in the semaphorin/plexin/neuropilin complex. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7m0r.cif.gz | 725.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7m0r.ent.gz | 575.3 KB | Display | PDB format |
PDBx/mmJSON format | 7m0r.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7m0r_validation.pdf.gz | 931 KB | Display | wwPDB validaton report |
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Full document | 7m0r_full_validation.pdf.gz | 1010.3 KB | Display | |
Data in XML | 7m0r_validation.xml.gz | 117.4 KB | Display | |
Data in CIF | 7m0r_validation.cif.gz | 181.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/m0/7m0r ftp://data.pdbj.org/pub/pdb/validation_reports/m0/7m0r | HTTPS FTP |
-Related structure data
Related structure data | 23613MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 64132.211 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Nrp1, Nrp / Production host: Homo sapiens (human) / References: UniProt: P97333 #2: Protein | Mass: 67931.812 Da / Num. of mol.: 2 / Mutation: A106K,551ARTRA555,731AAQAA735,758ANRA761 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Sema3a, Semad, SemD / Production host: Homo sapiens (human) / References: UniProt: O08665 #3: Protein | Mass: 133253.203 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Plxna4, Kiaa1550 / Production host: Homo sapiens (human) / References: UniProt: Q80UG2 #4: Chemical | ChemComp-CA / Has ligand of interest | N | Sequence details | The full sequence of Semaphorin-3A is NYANGKNNVPRLKLSYKEMLESNNVITFNGLANSSSYHTFLLDEERSRLYVGAKDHIFSF ...The full sequence of Semaphorin-3A is NYANGKNNVP | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Ternary complex of Sema3A, PlexinA4 and neuropilin 1 / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 600 kDa/nm / Experimental value: YES |
Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1453090 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26741 / Symmetry type: POINT |