[English] 日本語
Yorodumi- PDB-7mhz: Human Hedgehog acyltransferase (HHAT) in complex with a palmitoyl... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7mhz | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human Hedgehog acyltransferase (HHAT) in complex with a palmitoylated Hedgehog peptide product and a Fab antibody fragment | |||||||||
Components |
| |||||||||
Keywords | TRANSFERASE/IMMUNE SYSTEM / MBOAT / GOAT / porcupine / acyl transferase / membrane protein / membrane enzyme / ER / palmitoyl-CoA / TRANSFERASE-IMMUNE SYSTEM complex | |||||||||
Function / homology | Function and homology information N-terminal peptidyl-L-cysteine N-palmitoylation / morphogen activity / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation ...N-terminal peptidyl-L-cysteine N-palmitoylation / morphogen activity / positive regulation of skeletal muscle cell proliferation / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / hindgut morphogenesis / regulation of odontogenesis / positive regulation of mesenchymal cell proliferation involved in ureter development / trunk neural crest cell migration / Formation of lateral plate mesoderm / O-acyltransferase activity / polarity specification of anterior/posterior axis / striated muscle tissue development / negative regulation of alpha-beta T cell differentiation / regulation of glial cell proliferation / regulation of prostatic bud formation / ventral midline development / metanephric mesenchymal cell proliferation involved in metanephros development / formation of anatomical boundary / lung epithelium development / cholesterol-protein transferase activity / positive regulation of striated muscle cell differentiation / trachea morphogenesis / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / epithelial-mesenchymal cell signaling / Ligand-receptor interactions / laminin-1 binding / negative regulation of cholesterol efflux / salivary gland cavitation / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / negative regulation of mesenchymal cell apoptotic process / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / palmitoyltransferase activity / spinal cord motor neuron differentiation / cell development / positive regulation of T cell differentiation in thymus / Activation of SMO / cerebellar granule cell precursor proliferation / intermediate filament organization / prostate gland development / limb bud formation / lymphoid progenitor cell differentiation / lung lobe morphogenesis / mesenchymal cell apoptotic process / embryonic skeletal system development / establishment of epithelial cell polarity / skeletal muscle fiber differentiation / somite development / patched binding / embryonic digestive tract morphogenesis / neuron fate commitment / epithelial cell proliferation involved in salivary gland morphogenesis / animal organ formation / embryonic foregut morphogenesis / hindbrain development / ectoderm development / positive regulation of skeletal muscle tissue development / stem cell development / thalamus development / negative regulation of dopaminergic neuron differentiation / skeletal muscle cell proliferation / mesenchymal cell proliferation involved in lung development / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / positive regulation of immature T cell proliferation in thymus / dorsal/ventral neural tube patterning / negative thymic T cell selection / smooth muscle tissue development / self proteolysis / pattern specification process / male genitalia development / artery development / positive regulation of astrocyte differentiation / oligodendrocyte development / regulation of stem cell proliferation / epithelial cell proliferation involved in prostate gland development / embryonic pattern specification / positive regulation of epithelial cell proliferation involved in prostate gland development / branching involved in salivary gland morphogenesis / Release of Hh-Np from the secreting cell / dopaminergic neuron differentiation / lung-associated mesenchyme development / intein-mediated protein splicing / Formation of axial mesoderm / regulation of proteolysis / metanephric collecting duct development / glycosaminoglycan binding / metanephros development Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Mus musculus (house mouse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Long, S.B. / Jiang, Y. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Science / Year: 2021 Title: Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT. Authors: Yiyang Jiang / Thomas L Benz / Stephen B Long / Abstract: Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino- ...Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7mhz.cif.gz | 169.6 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7mhz.ent.gz | 120 KB | Display | PDB format |
PDBx/mmJSON format | 7mhz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mhz_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7mhz_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7mhz_validation.xml.gz | 30.3 KB | Display | |
Data in CIF | 7mhz_validation.cif.gz | 43.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mh/7mhz ftp://data.pdbj.org/pub/pdb/validation_reports/mh/7mhz | HTTPS FTP |
-Related structure data
Related structure data | 23837MC 7mhyC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Antibody , 2 types, 2 molecules OP
#3: Antibody | Mass: 51307.891 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
---|---|
#4: Antibody | Mass: 22868.863 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Production host: Mus musculus (house mouse) |
-Protein/peptide / Protein , 2 types, 2 molecules BA
#1: Protein/peptide | Mass: 750.848 Da / Num. of mol.: 1 / Fragment: UNP residues 24-31 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q15465 |
---|---|
#2: Protein | Mass: 57358.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: HHAT, MART2, SKI1 / Production host: Homo sapiens (human) References: UniProt: Q5VTY9, Transferases; Acyltransferases; Transferring groups other than aminoacyl groups |
-Non-polymers , 4 types, 15 molecules
#5: Chemical | ChemComp-PLM / | ||
---|---|---|---|
#6: Chemical | ChemComp-HEM / | ||
#7: Chemical | #8: Chemical | ChemComp-AJP / |
-Details
Has ligand of interest | Y |
---|---|
Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: HHAT in complex with a palmitoylated Hedgehog peptide product and a Fab antibody fragment Type: COMPLEX / Entity ID: #1-#4 / Source: MULTIPLE SOURCES |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Mus musculus (house mouse) |
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 |
---|---|
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 |
Image recording | Electron dose: 43.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 142121 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 112.57 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|