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Open data
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Basic information
Entry | Database: PDB / ID: 9n4k | ||||||
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Title | CryoEM structure of ALK2-ActRIIB bound to BMP6 | ||||||
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![]() | SIGNALING PROTEIN / TGFB / Signaling / Receptor / Bone Morphogenetic Protein / ALK2 / Ligand / Growth Factor | ||||||
Function / homology | ![]() positive regulation of aldosterone biosynthetic process / positive regulation of aldosterone secretion / Regulation of signaling by NODAL / activin receptor activity / activin receptor activity, type II / lymphatic endothelial cell differentiation / positive regulation of activin receptor signaling pathway / enzyme activator complex / venous blood vessel development / negative regulation of adherens junction organization ...positive regulation of aldosterone biosynthetic process / positive regulation of aldosterone secretion / Regulation of signaling by NODAL / activin receptor activity / activin receptor activity, type II / lymphatic endothelial cell differentiation / positive regulation of activin receptor signaling pathway / enzyme activator complex / venous blood vessel development / negative regulation of adherens junction organization / endocardial cushion cell fate commitment / positive regulation of chondrocyte differentiation / lymphangiogenesis / trophoblast cell migration / mitral valve morphogenesis / BMP receptor complex / cardiac muscle cell fate commitment / BMP receptor activity / atrial septum primum morphogenesis / endocardial cushion fusion / retina vasculature development in camera-type eye / positive regulation of endothelial cell differentiation / positive regulation of cardiac epithelial to mesenchymal transition / acute inflammatory response / positive regulation of determination of dorsal identity / type B pancreatic cell development / transforming growth factor beta receptor activity, type I / embryonic foregut morphogenesis / BMP receptor binding / smooth muscle cell differentiation / activin receptor complex / activin receptor activity, type I / endocardial cushion formation / artery development / eye development / endochondral ossification / pharyngeal system development / transmembrane receptor protein serine/threonine kinase activity / receptor protein serine/threonine kinase / activin binding / pattern specification process / cellular response to BMP stimulus / Signaling by BMP / male genitalia development / Signaling by Activin / negative regulation of cell-cell adhesion mediated by cadherin / positive regulation of vascular permeability / activin receptor signaling pathway / negative regulation of activin receptor signaling pathway / Signaling by NODAL / embryonic heart tube morphogenesis / gastrulation with mouth forming second / positive regulation of lipopolysaccharide-mediated signaling pathway / pancreas development / dorsal/ventral pattern formation / transforming growth factor beta binding / cartilage development / kinase activator activity / determination of left/right symmetry / negative regulation of ossification / atrioventricular valve morphogenesis / neural crest cell migration / anterior/posterior pattern specification / negative regulation of cold-induced thermogenesis / cell surface receptor protein serine/threonine kinase signaling pathway / insulin secretion / skeletal system morphogenesis / organ growth / growth factor binding / branching involved in blood vessel morphogenesis / ventricular septum morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / SMAD binding / odontogenesis of dentin-containing tooth / mesoderm development / germ cell development / roof of mouth development / peptide hormone binding / positive regulation of intracellular signal transduction / response to magnesium ion / mesoderm formation / positive regulation of SMAD protein signal transduction / regulation of ossification / blood vessel remodeling / response to retinoic acid / positive regulation of osteoblast differentiation / positive regulation of bone mineralization / response to glucose / negative regulation of signal transduction / BMP signaling pathway / positive regulation of endothelial cell proliferation / positive regulation of neuron differentiation / protein serine/threonine/tyrosine kinase activity / transforming growth factor beta receptor signaling pathway / lung development / protein tyrosine kinase binding / response to glucocorticoid / cytokine activity / positive regulation of epithelial cell proliferation / response to activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Goebel, E.J. / Saotome, K. / Franklin, M.C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: CryoEM structure of ALK2:BMP6 reveals distinct mechanism that allow ALK2 to interact with both BMP and activin ligands. Authors: Erich J Goebel / Senem Aykul / Warren W Hom / Kei Saotome / Aris N Economides / Matthew C Franklin / Vincent J Idone / ![]() Abstract: Ligands in the transforming growth factor β (TGF-β) family [activins, Bone Morphogenetic Proteins (BMPs), and TGF-βs] signal by bringing together two type I and two type II receptors. Activin ...Ligands in the transforming growth factor β (TGF-β) family [activins, Bone Morphogenetic Proteins (BMPs), and TGF-βs] signal by bringing together two type I and two type II receptors. Activin receptor-like kinase-2 (ALK2) is the only type I receptor among the seven TGF-β type I receptors that interacts with both activin and BMP ligands. With BMPs, ALK2 acts as a signaling receptor to activate small mothers against decapentaplegic 1 (SMAD1)/5/8 signaling. Alternatively, with activins, such as Activin A (ActA), ALK2 forms nonsignaling complexes that negatively regulate ALK2 and ActA signaling. To gain insight into how ALK2 interacts with two distinct classes of ligands, we resolved the cryoelectron microscopy structure of ALK2 in complex with the type II receptor, ActRIIB, and the ligand, BMP6, in parallel with the corresponding structure with ALK3 for direct comparison. These structures demonstrate that ALK2 and ALK3 utilize different mechanisms to interact with BMP6 at the wrist interface, with ALK2 relying on BMP6 glycosylation and ALK3 relying on a salt bridge. Modeling of ALK2:ActA reveals that binding relies on ActA's fingertip region, mirroring the interaction of ActA with its other receptor, ALK4. Our results demonstrate that ALK2 is a "hybrid" receptor that incorporates features of BMP type I receptors such as ALK3 at the wrist interface and an activin type I receptor such as ALK4 at the fingertip. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 130.1 KB | Display | ![]() |
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PDB format | ![]() | 98.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 28.8 KB | Display | |
Data in CIF | ![]() | 40.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 48883MC ![]() 9mirC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Activin receptor type- ... , 2 types, 4 molecules AFCD
#1: Protein | Mass: 14933.380 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q13705, receptor protein serine/threonine kinase #3: Protein | Mass: 13189.880 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q04771, receptor protein serine/threonine kinase |
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-Protein , 1 types, 2 molecules BE
#2: Protein | Mass: 15695.711 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Sugars , 3 types, 10 molecules 


#4: Polysaccharide | #5: Sugar | ChemComp-NAG / #6: Sugar | |
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-Details
Has ligand of interest | N |
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Has protein modification | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Ternary complex of ALK2-ActRIIB with BMP6 / Type: COMPLEX / Details: ALK2-ActRIIB fused by Antibody Hinge region / Entity ID: #1-#3 / Source: RECOMBINANT | |||||||||||||||
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Molecular weight | Value: 0.08 MDa / Experimental value: NO | |||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||
Buffer solution | pH: 7.5 / Details: 50mM Tris-HCL, 100mM NaCl | |||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Sample was mono disperse following purification over size exclusion chromatography. | |||||||||||||||
Specimen support | Grid material: GOLD | |||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 800 nm / Alignment procedure: BASIC |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
EM software | Name: PHENIX / Version: 1.21.2_5419 / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 42185 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL Details: Initial fitting was performed in ChimeraX and real-space refinement was carried out within Phenix. | ||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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