View source for 5wno


==Crystal structure of C. elegans LET-23 kinase domain complexed with AMP-PNP==
<StructureSection load='5wno' size='340' side='right'caption='[[5wno]], [[Resolution|resolution]] 2.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wno]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WNO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.386&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5wno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wno OCA], [https://pdbe.org/5wno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wno RCSB], [https://www.ebi.ac.uk/pdbsum/5wno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wno ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LET23_CAEEL LET23_CAEEL] Tyrosine-protein kinase receptor which, upon binding ligand lin-3, activates 2 signaling cascades: the let-60/Ras and MAP kinase signaling pathway and the let-60-independent phospholipase C-mediated Ca(2+) signaling pathway. Each pathway regulates distinct functions. By activating let-60/Ras, regulates larval development, induction of vulva cell precursors during vulva development, male spicule formation and posterior development of the epidermis (PubMed:2071015, PubMed:8313880, PubMed:9491893). Probably by activating phospholipase plc-3 and inositol 1,4,5-trisphosphate receptor itr-1 signaling cascade downstream of ligand lin-3, plays a role in ovulation by promoting ovulatory gonadal sheath cell contractions (PubMed:9491893, PubMed:15194811). Probably by regulating neuronal transmission in ALA neurons, mediates, independently of let-60/Ras, the decrease in pharyngeal pumping and locomotion during the quiescent state that precedes each larval molt, downstream of lin-3 and upstream of plc-3 (PubMed:17891142).<ref>PMID:15194811</ref> <ref>PMID:17891142</ref> <ref>PMID:2071015</ref> <ref>PMID:8313880</ref> <ref>PMID:9491893</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23.,Liu L, Thaker TM, Freed DM, Frazier N, Malhotra K, Lemmon MA, Jura N Structure. 2018 Feb 6;26(2):270-281.e4. doi: 10.1016/j.str.2017.12.012. Epub 2018, Jan 18. PMID:29358026<ref>PMID:29358026</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wno" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Large Structures]]
[[Category: Jura N]]
[[Category: Liu L]]
[[Category: Thaker TM]]