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5wno

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Revision as of 06:39, 18 April 2018

Crystal structure of C. elegans LET-23 kinase domain complexed with AMP-PNP

Structural highlights

5wno is a 1 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	let-23, kin-7, ZK1067.1 (CAEEL)
Activity:	Receptor protein-tyrosine kinase, with EC number 2.7.10.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yin X, Gower NJ, Baylis HA, Strange K. Inositol 1,4,5-trisphosphate signaling regulates rhythmic contractile activity of myoepithelial sheath cells in Caenorhabditis elegans. Mol Biol Cell. 2004 Aug;15(8):3938-49. doi: 10.1091/mbc.E04-03-0198. Epub 2004, Jun 11. PMID:15194811 doi:http://dx.doi.org/10.1091/mbc.E04-03-0198
↑ Van Buskirk C, Sternberg PW. Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans. Nat Neurosci. 2007 Oct;10(10):1300-7. doi: 10.1038/nn1981. Epub 2007 Sep 23. PMID:17891142 doi:http://dx.doi.org/10.1038/nn1981
↑ Aroian RV, Sternberg PW. Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction. Genetics. 1991 Jun;128(2):251-67. PMID:2071015
↑ Aroian RV, Lesa GM, Sternberg PW. Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function. EMBO J. 1994 Jan 15;13(2):360-6. PMID:8313880
↑ Clandinin TR, DeModena JA, Sternberg PW. Inositol trisphosphate mediates a RAS-independent response to LET-23 receptor tyrosine kinase activation in C. elegans. Cell. 1998 Feb 20;92(4):523-33. PMID:9491893
↑ Liu L, Thaker TM, Freed DM, Frazier N, Malhotra K, Lemmon MA, Jura N. Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23. Structure. 2018 Feb 6;26(2):270-281.e4. doi: 10.1016/j.str.2017.12.012. Epub 2018, Jan 18. PMID:29358026 doi:http://dx.doi.org/10.1016/j.str.2017.12.012

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5wno"

@@ Line 3: / Line 3: @@
 <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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WNO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wno]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WNO FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">let-23, kin-7, ZK1067.1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wno OCA], [http://pdbe.org/5wno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wno RCSB], [http://www.ebi.ac.uk/pdbsum/5wno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wno ProSAT]</span></td></tr>
@@ Line 10: / Line 11: @@
 == Function ==
 [[http://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: Caeel]]
 [[Category: Receptor protein-tyrosine kinase]]
 [[Category: Jura, N]]

5wno

From Proteopedia

Revision as of 06:39, 18 April 2018

Crystal structure of C. elegans LET-23 kinase domain complexed with AMP-PNP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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