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Basic information
Entry | Database: PDB / ID: 7aml | ||||||
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Title | RET/GDNF/GFRa1 extracellular complex Cryo-EM structure | ||||||
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![]() | SIGNALING PROTEIN / VERTEBRATE DEVELOPMENT / PART OF THE RET-GFL-GFRA COMPLEX / NEUROTROPHIC FACTOR | ||||||
Function / homology | ![]() branchiomeric skeletal muscle development / pronephros morphogenesis / RAF/MAP kinase cascade / : / diencephalon development / positive regulation of ureteric bud formation / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / regulation of dopaminergic neuron differentiation / glial cell-derived neurotrophic factor receptor binding ...branchiomeric skeletal muscle development / pronephros morphogenesis / RAF/MAP kinase cascade / : / diencephalon development / positive regulation of ureteric bud formation / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / regulation of dopaminergic neuron differentiation / glial cell-derived neurotrophic factor receptor binding / glial cell-derived neurotrophic factor receptor signaling pathway / regulation of morphogenesis of a branching structure / regulation of dopamine uptake involved in synaptic transmission / enteric nervous system development / neural crest cell migration involved in autonomic nervous system development / peristalsis / positive regulation of branching involved in ureteric bud morphogenesis / sympathetic nervous system development / peripheral nervous system development / metanephros development / axon extension / mRNA stabilization / positive regulation of kinase activity / neural crest cell migration / MAP kinase kinase kinase activity / branching involved in ureteric bud morphogenesis / homophilic cell adhesion via plasma membrane adhesion molecules / transmembrane receptor protein tyrosine kinase activity / cell surface receptor protein tyrosine kinase signaling pathway / receptor protein-tyrosine kinase / growth factor activity / receptor tyrosine kinase binding / neuron projection development / signaling receptor activity / nervous system development / protein-containing complex assembly / negative regulation of neuron apoptotic process / receptor complex / membrane raft / external side of plasma membrane / axon / calcium ion binding / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / extracellular space / extracellular region / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Adams, S.E. / Earl, C.P. / Purkiss, A.G. / McDonald, N.Q. | ||||||
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![]() | ![]() Title: A two-site flexible clamp mechanism for RET-GDNF-GFRα1 assembly reveals both conformational adaptation and strict geometric spacing. Authors: Sarah E Adams / Andrew G Purkiss / Phillip P Knowles / Andrea Nans / David C Briggs / Annabel Borg / Christopher P Earl / Kerry M Goodman / Agata Nawrotek / Aaron J Borg / Pauline B McIntosh ...Authors: Sarah E Adams / Andrew G Purkiss / Phillip P Knowles / Andrea Nans / David C Briggs / Annabel Borg / Christopher P Earl / Kerry M Goodman / Agata Nawrotek / Aaron J Borg / Pauline B McIntosh / Francesca M Houghton / Svend Kjær / Neil Q McDonald / ![]() Abstract: RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. GDNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognize and activate RET ...RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. GDNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognize and activate RET stimulating its cytoplasmic kinase function. The principles for RET ligand-co-receptor recognition are incompletely understood. Here, we report a crystal structure of the cadherin-like module (CLD1-4) from zebrafish RET revealing interdomain flexibility between CLD2 and CLD3. Comparison with a cryo-electron microscopy structure of a ligand-engaged zebrafish RET-GDNF-GFRα1a complex indicates conformational changes within a clade-specific CLD3 loop adjacent to the co-receptor. Our observations indicate that RET is a molecular clamp with a flexible calcium-dependent arm that adapts to different GFRα co-receptors, while its rigid arm recognizes a GFL dimer to align both membrane-proximal cysteine-rich domains. We also visualize linear arrays of RET-GDNF-GFRα1a suggesting that a conserved contact stabilizes higher-order species. Our study reveals that ligand-co-receptor recognition by RET involves both receptor plasticity and strict spacing of receptor dimers by GFL ligands. | ||||||
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-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 71.6 KB | Display | |
Data in CIF | ![]() | 104.9 KB | Display | |
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-Related structure data
Related structure data | ![]() 11822MC ![]() 7ab8C ![]() 7amkC C: citing same article ( M: map data used to model this data |
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Similar structure data |
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Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
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