7bhe
From Proteopedia
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| - | ==== | + | ==DARPin_D5/Her3 domain 4 complex, monoclinic crystals== |
| - | <StructureSection load='7bhe' size='340' side='right'caption='[[7bhe]]' scene=''> | + | <StructureSection load='7bhe' size='340' side='right'caption='[[7bhe]], [[Resolution|resolution]] 2.30Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7bhe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BHE 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=7bhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bhe OCA], [https://pdbe.org/7bhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bhe RCSB], [https://www.ebi.ac.uk/pdbsum/7bhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bhe 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]] 2.297Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7bhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bhe OCA], [https://pdbe.org/7bhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bhe RCSB], [https://www.ebi.ac.uk/pdbsum/7bhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bhe ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN] Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:[https://omim.org/entry/607598 607598]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology.<ref>PMID:17701904</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN] Binds and is activated by neuregulins and NTAK.<ref>PMID:15358134</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The members of the human epidermal growth factor receptor (HER) family are among the most intensely studied oncological targets. HER3 (ErbB3), which had long been neglected, has emerged as a key oncogene, regulating the activity of other receptors and being involved in progression and tumor escape in multiple types of cancer. Designed ankyrin-repeat proteins (DARPins) serve as antibody mimetics that have proven to be useful in the clinic, in diagnostics and in research. DARPins have previously been selected against EGFR (HER1), HER2 and HER4. In particular, their combination into bivalent binders that separate or lock receptors in their inactive conformation has proved to be a promising strategy for the design of potent anticancer therapeutics. Here, the selection of DARPins targeting extracellular domain 4 of HER3 (HER3d4) is described. One of the selected DARPins, D5, in complex with HER3d4 crystallized in two closely related crystal forms that diffracted to 2.3 and 2.0 A resolution, respectively. The DARPin D5 epitope comprises HER3d4 residues 568-577. These residues also contribute to interactions within the tethered (inactive) and extended (active) conformations of the extracellular domain of HER3. | ||
| + | |||
| + | Crystal structures of HER3 extracellular domain 4 in complex with the designed ankyrin-repeat protein D5.,Radom F, Vonrhein C, Mittl PRE, Pluckthun A Acta Crystallogr F Struct Biol Commun. 2021 Jul 1;77(Pt 7):192-201. doi: , 10.1107/S2053230X21006002. Epub 2021 Jun 29. PMID:34196609<ref>PMID:34196609</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7bhe" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Mittl PRE]] | ||
| + | [[Category: Pluckthun A]] | ||
| + | [[Category: Radom F]] | ||
Revision as of 12:28, 1 February 2024
DARPin_D5/Her3 domain 4 complex, monoclinic crystals
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