[English] 日本語
![](img/lk-miru.gif)
- EMDB-23836: Human Hedgehog acyltransferase (HHAT) in complex with palmitoyl-C... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-23836 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human Hedgehog acyltransferase (HHAT) in complex with palmitoyl-CoA and two Fab antibody fragments | |||||||||
![]() | final map | |||||||||
![]() |
| |||||||||
Function / homology | ![]() N-terminal peptidyl-L-cysteine N-palmitoylation / O-acyltransferase activity / HHAT G278V doesn't palmitoylate Hh-Np / palmitoyltransferase activity / smoothened signaling pathway / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / Hedgehog ligand biogenesis / Golgi membrane / endoplasmic reticulum membrane / GTP binding ...N-terminal peptidyl-L-cysteine N-palmitoylation / O-acyltransferase activity / HHAT G278V doesn't palmitoylate Hh-Np / palmitoyltransferase activity / smoothened signaling pathway / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / Hedgehog ligand biogenesis / Golgi membrane / endoplasmic reticulum membrane / GTP binding / Golgi apparatus / endoplasmic reticulum Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.7 Å | |||||||||
![]() | Long SB / Jiang Y | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 47.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 15.6 KB 15.6 KB | Display Display | ![]() |
Images | ![]() | 157.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 350 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 349.6 KB | Display | |
Data in XML | ![]() | 7.5 KB | Display | |
Data in CIF | ![]() | 8.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7mhyMC ![]() 7mhzC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | final map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.532 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
+Entire : HHAT in complex with palmitoyl-CoA and two Fab antibody fragments
+Supramolecule #1: HHAT in complex with palmitoyl-CoA and two Fab antibody fragments
+Macromolecule #1: Protein-cysteine N-palmitoyltransferase HHAT
+Macromolecule #2: 1C06 Fab heavy chain
+Macromolecule #3: 1C06 Fab light chain
+Macromolecule #4: 3H02 Fab heavy chain
+Macromolecule #5: 3H02 Fab light chain
+Macromolecule #6: PROTOPORPHYRIN IX CONTAINING FE
+Macromolecule #7: Palmitoyl-CoA
+Macromolecule #8: Digitonin
+Macromolecule #9: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.5 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 26.5 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 2.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 174058 |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |