7nbi
From Proteopedia
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==Crystal structure of a monomeric FLT3 Ligand variant== | ==Crystal structure of a monomeric FLT3 Ligand variant== | ||
| - | <StructureSection load='7nbi' size='340' side='right'caption='[[7nbi]]' scene=''> | + | <StructureSection load='7nbi' size='340' side='right'caption='[[7nbi]], [[Resolution|resolution]] 1.65Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NBI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7nbi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NBI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NBI FirstGlance]. <br> |
| - | </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=7nbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nbi OCA], [https://pdbe.org/7nbi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nbi RCSB], [https://www.ebi.ac.uk/pdbsum/7nbi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nbi ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7nbi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nbi OCA], [https://pdbe.org/7nbi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nbi RCSB], [https://www.ebi.ac.uk/pdbsum/7nbi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nbi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FLT3L_HUMAN FLT3L_HUMAN] Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The overarching paradigm for the activation of class III and V receptor tyrosine kinases (RTKs) prescribes cytokine-mediated dimerization of the receptor ectodomains and homotypic receptor-receptor interactions. However, structural studies have shown that the hematopoietic receptor FLT3, a class III RTK, does not appear to engage in such receptor-receptor contacts, despite its efficient dimerization by dimeric FLT3 ligand (FL). As part of efforts to better understand the intricacies of FLT3 activation, we sought to engineer a monomeric FL. It was found that a Leu27Asp substitution at the dimer interface of the cytokine led to a stable monomeric cytokine (FLL27D) without abrogation of receptor binding. The crystal structure of FLL27D at 1.65 A resolution revealed that the introduced point mutation led to shielding of the hydrophobic footprint of the dimerization interface in wild-type FL without affecting the conformation of the FLT3 binding site. Thus, FLL27D can serve as a monomeric FL variant to further interrogate the assembly mechanism of extracellular complexes of FLT3 in physiology and disease. | ||
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| + | Engineering and crystal structure of a monomeric FLT3 ligand variant.,Pannecoucke E, Raes L, Savvides SN Acta Crystallogr F Struct Biol Commun. 2021 Apr 1;77(Pt 4):121-127. doi:, 10.1107/S2053230X21003289. Epub 2021 Apr 6. PMID:33830077<ref>PMID:33830077</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7nbi" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Pannecoucke E]] | [[Category: Pannecoucke E]] | ||
[[Category: Raes L]] | [[Category: Raes L]] | ||
[[Category: Savvides SN]] | [[Category: Savvides SN]] | ||
Current revision
Crystal structure of a monomeric FLT3 Ligand variant
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