5WNO
Crystal structure of C. elegans LET-23 kinase domain complexed with AMP-PNP
Summary for 5WNO
| Entry DOI | 10.2210/pdb5wno/pdb |
| Descriptor | Receptor tyrosine-protein kinase let-23, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | receptor tyrosine-protein kinase, dimerization, inactive conformation, cell signaling, let-23, c. elegans, transferase |
| Biological source | Caenorhabditis elegans |
| Total number of polymer chains | 1 |
| Total formula weight | 38480.11 |
| Authors | Liu, L.,Thaker, T.M.,Jura, N. (deposition date: 2017-08-01, release date: 2018-01-31, Last modification date: 2024-12-25) |
| Primary citation | Liu, L.,Thaker, T.M.,Freed, D.M.,Frazier, N.,Malhotra, K.,Lemmon, M.A.,Jura, N. Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23. Structure, 26:270-281.e4, 2018 Cited by PubMed Abstract: In the active HER receptor dimers, kinases play distinct roles; one is the catalytically active kinase and the other is its allosteric activator. This specialization enables signaling by the catalytically inactive HER3, which functions exclusively as an allosteric activator upon heterodimerization with other HER receptors. It is unclear whether the allosteric activation mechanism evolved before HER receptors functionally specialized. We determined the crystal structure of the kinase domain of the only EGF receptor in Caenorhabditis elegans, LET-23. Our structure of a non-human EGFR kinase reveals autoinhibitory features conserved in the human counterpart. Strikingly, mutations within the putative allosteric dimer interface abrogate activity of the isolated LET-23 kinase and of the full-length receptor despite these regions being only partially conserved with human EGFR. Our results indicate that ancestral EGFRs have built-in features that poise them for allosteric activation that could facilitate emergence of the catalytically dead, yet functional, orthologs. PubMed: 29358026DOI: 10.1016/j.str.2017.12.012 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.386 Å) |
Structure validation
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