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Basic information
Entry | Database: PDB / ID: 9mir | ||||||
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Title | CryoEM structure of ALK3-ActRIIB bound to BMP6 | ||||||
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![]() | SIGNALING PROTEIN / Signaling / Ligand / Complex / Receptor / Type I / Type II / TGFB / BMP | ||||||
Function / homology | ![]() neural plate mediolateral regionalization / paraxial mesoderm structural organization / positive regulation of cardiac ventricle development / fibrous ring of heart morphogenesis / positive regulation of transforming growth factor beta2 production / Mullerian duct regression / heart formation / atrioventricular node cell development / mesendoderm development / dorsal aorta morphogenesis ...neural plate mediolateral regionalization / paraxial mesoderm structural organization / positive regulation of cardiac ventricle development / fibrous ring of heart morphogenesis / positive regulation of transforming growth factor beta2 production / Mullerian duct regression / heart formation / atrioventricular node cell development / mesendoderm development / dorsal aorta morphogenesis / tricuspid valve morphogenesis / cardiac right ventricle morphogenesis / BMP binding / hindlimb morphogenesis / negative regulation of muscle cell differentiation / pharyngeal arch artery morphogenesis / regulation of lateral mesodermal cell fate specification / lateral mesoderm development / pituitary gland development / mitral valve morphogenesis / negative regulation of smooth muscle cell migration / BMP receptor activity / regulation of cellular senescence / ventricular compact myocardium morphogenesis / dorsal/ventral axis specification / neural crest cell development / transforming growth factor beta receptor activity, type I / ectoderm development / endocardial cushion formation / receptor protein serine/threonine kinase / ventricular trabecula myocardium morphogenesis / outflow tract septum morphogenesis / central nervous system neuron differentiation / positive regulation of mesenchymal cell proliferation / embryonic digit morphogenesis / ventricular septum morphogenesis / SMAD binding / odontogenesis of dentin-containing tooth / roof of mouth development / mesoderm formation / positive regulation of SMAD protein signal transduction / somatic stem cell population maintenance / developmental growth / chondrocyte differentiation / embryonic organ development / positive regulation of osteoblast differentiation / positive regulation of bone mineralization / somitogenesis / positive regulation of cardiac muscle cell proliferation / positive regulation of vascular associated smooth muscle cell proliferation / transforming growth factor beta receptor signaling pathway / lung development / epithelial cell proliferation / positive regulation of epithelial cell proliferation / caveola / negative regulation of neurogenesis / positive regulation of miRNA transcription / osteoblast differentiation / angiogenesis / in utero embryonic development / receptor complex / immune response / negative regulation of gene expression / external side of plasma membrane / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / ATP binding / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||
![]() | Goebel, E.J. / Saotome, K. / Franklin, M.C. | ||||||
Funding support | 1items
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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. | ||||||
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-Validation report
Summary document | ![]() | 1.5 MB | Display | ![]() |
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Full document | ![]() | 1.5 MB | Display | |
Data in XML | ![]() | 30.7 KB | Display | |
Data in CIF | ![]() | 42.8 KB | Display | |
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-Related structure data
Related structure data | ![]() 48301MC ![]() 9n4kC 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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Noncrystallographic symmetry (NCS) | NCS domain:
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