Loading
PDBj
MenuPDBj@FacebookPDBj@TwitterPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

7AMK

Zebrafish RET Cadherin Like Domains 1 to 4.

Summary for 7AMK
Entry DOI10.2210/pdb7amk/pdb
Related7AB8
DescriptorProto-oncogene tyrosine-protein kinase receptor Ret, GLYCEROL, TRIETHYLENE GLYCOL, ... (14 entities in total)
Functional Keywordsligand recognition, receptor tyrosine kinase, glycosylation, signaling protein
Biological sourceDanio rerio (Zebrafish)
Total number of polymer chains2
Total formula weight118656.03
Authors
Purkiss, A.G.,McDonald, N.Q.,Goodman, K.M.,Narowtek, A.,Knowles, P.P. (deposition date: 2020-10-09, release date: 2021-02-03, Last modification date: 2024-10-16)
Primary citationAdams, S.E.,Purkiss, A.G.,Knowles, P.P.,Nans, A.,Briggs, D.C.,Borg, A.,Earl, C.P.,Goodman, K.M.,Nawrotek, A.,Borg, A.J.,McIntosh, P.B.,Houghton, F.M.,Kjaer, S.,McDonald, N.Q.
A two-site flexible clamp mechanism for RET-GDNF-GFR alpha 1 assembly reveals both conformational adaptation and strict geometric spacing.
Structure, 29:694-, 2021
Cited by
PubMed 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 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.
PubMed: 33484636
DOI: 10.1016/j.str.2020.12.012
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.2 Å)
Structure validation

227111

PDB entries from 2024-11-06

PDB statisticsPDBj update infoContact PDBjnumon