+Open data
-Basic information
Entry | Database: PDB / ID: 8bbg | |||||||||||||||
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Title | Structure of the IFT-A complex; anterograde IFT-A train model | |||||||||||||||
Components |
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Keywords | TRANSPORT PROTEIN / cilia / intraflagellar transport / membrane protein import / complex | |||||||||||||||
Function / homology | Function and homology information smoothened signaling pathway involved in dorsal/ventral neural tube patterning / myotome development / protein localization to non-motile cilium / regulation of intraciliary retrograde transport / forebrain dorsal/ventral pattern formation / ear morphogenesis / intraciliary anterograde transport / cone photoreceptor outer segment / negative regulation of eating behavior / digestive system development ...smoothened signaling pathway involved in dorsal/ventral neural tube patterning / myotome development / protein localization to non-motile cilium / regulation of intraciliary retrograde transport / forebrain dorsal/ventral pattern formation / ear morphogenesis / intraciliary anterograde transport / cone photoreceptor outer segment / negative regulation of eating behavior / digestive system development / intraciliary transport particle A / embryonic heart tube left/right pattern formation / embryonic body morphogenesis / neural tube patterning / photoreceptor cell outer segment organization / protein localization to ciliary membrane / cerebellar Purkinje cell differentiation / intraciliary retrograde transport / establishment of protein localization to organelle / embryonic camera-type eye development / intraciliary transport / gonad development / spinal cord dorsal/ventral patterning / regulation of cilium assembly / photoreceptor connecting cilium / ciliary tip / ventricular system development / Intraflagellar transport / camera-type eye morphogenesis / embryonic brain development / non-motile cilium assembly / protein localization to cilium / regulation of smoothened signaling pathway / embryonic heart tube development / embryonic cranial skeleton morphogenesis / non-motile cilium / embryonic forelimb morphogenesis / motile cilium / nervous system process / determination of left/right symmetry / embryonic limb morphogenesis / limb development / smoothened signaling pathway / embryonic digit morphogenesis / receptor clustering / axoneme / Bergmann glial cell differentiation / centriolar satellite / photoreceptor outer segment / cilium assembly / Hedgehog 'off' state / negative regulation of smoothened signaling pathway / centriole / ciliary basal body / cellular response to leukemia inhibitory factor / neural tube closure / cell morphogenesis / cilium / microtubule cytoskeleton / positive regulation of canonical Wnt signaling pathway / heart development / protein-containing complex assembly / in utero embryonic development / cytoskeleton / intracellular signal transduction / centrosome / chromatin binding / positive regulation of gene expression / regulation of transcription by RNA polymerase II / membrane / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||
Authors | Hesketh, S.J. / Mukhopadhyay, A.G. / Nakamura, D. / Toropova, K. / Roberts, A.J. | |||||||||||||||
Funding support | United Kingdom, 4items
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Citation | Journal: Cell / Year: 2022 Title: IFT-A structure reveals carriages for membrane protein transport into cilia. Authors: Sophie J Hesketh / Aakash G Mukhopadhyay / Dai Nakamura / Katerina Toropova / Anthony J Roberts / Abstract: Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) ...Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of β-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-A⋅TULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8bbg.cif.gz | 1.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8bbg.ent.gz | 920.1 KB | Display | PDB format |
PDBx/mmJSON format | 8bbg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8bbg_validation.pdf.gz | 704.8 KB | Display | wwPDB validaton report |
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Full document | 8bbg_full_validation.pdf.gz | 730.5 KB | Display | |
Data in XML | 8bbg_validation.xml.gz | 122.8 KB | Display | |
Data in CIF | 8bbg_validation.cif.gz | 214.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bb/8bbg ftp://data.pdbj.org/pub/pdb/validation_reports/bb/8bbg | HTTPS FTP |
-Related structure data
Related structure data | 4304M 8bbeC 8bbfC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-WD repeat-containing protein ... , 2 types, 2 molecules AE
#1: Protein | Mass: 153639.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR19, IFT144, KIAA1638 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8NEZ3 |
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#5: Protein | Mass: 134037.969 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: WDR35, IFT121, KIAA1336 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9P2L0 |
-Intraflagellar transport protein ... , 3 types, 3 molecules BCF
#2: Protein | Mass: 167328.312 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IFT140, KIAA0590, WDTC2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96RY7 |
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#3: Protein | Mass: 142007.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IFT122, SPG, WDR10, WDR140 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9HBG6 |
#6: Protein | Mass: 23615.119 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: IFT43, C14orf179 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96FT9 |
-Protein , 1 types, 1 molecules D
#4: Protein | Mass: 170652.609 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MGMT, TTC21B, IFT139, KIAA1992, Nbla10696 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q7Z4L5, methylated-DNA-[protein]-cysteine S-methyltransferase |
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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: IFT-A complex / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
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 / Nominal defocus max: 3500 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 48 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) Details: Average electron dose for additional dataset was 49.5 (e-/A2) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 242645 Details: Above value for the IFT-A2 module map (EMD-15954), resolution range 3.2-8A. For the IFT-A1 module map (EMD-15955), number of particles used was 136617 with map resolution range 7-15 A. Symmetry type: POINT |
Atomic model building | Details: To generate a 14 subunit IFT-A train polymer from PDB-8BBG please enter the following in the command line of ChimeraX: sym #1 biomt copies true newModel true |