View source for 9pi9


==Sacituzumab Fab bound to Trop2 Dimer==
<StructureSection load='9pi9' size='340' side='right'caption='[[9pi9]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9pi9]] is a 6 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=9PI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PI9 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]] 1.56&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=9pi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pi9 OCA], [https://pdbe.org/9pi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pi9 RCSB], [https://www.ebi.ac.uk/pdbsum/9pi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pi9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TACD2_HUMAN TACD2_HUMAN] Honey-droplet corneal dystrophy;Gelatinous drop-like corneal dystrophy. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/TACD2_HUMAN TACD2_HUMAN] May function as a growth factor receptor.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sacituzumab govitecan (SG) is a therapeutic antibody-drug conjugate globally approved for the treatment of breast cancer. SG targets the trophoblast cell-surface antigen-2 (Trop2) at the surface of cancer cells to deliver the cytotoxic topoisomerase I inhibitor SN-38 to the tumor microenvironment. SN-38 is covalently linked to the humanized monoclonal antibody (mAb) sacituzumab via a hydrolyzable linker. Here, we describe the 1.56-A X-ray crystal structure and stoichiometry of the human Trop2 ectodomain in complex with a sacituzumab (hRS7) antigen-binding Fab fragment. The complex reveals a 2:2 stoichiometry where two sacituzumab Fabs bind across the two Trop2 dimer subunits, inducing a conformational change compared to the apo-structure. Cryo-electron microscopy (cryoEM) and size-exclusion chromatography in combination with multi-angle light scattering (SEC-MALS) analysis of the intact sacituzumab mAb bound to the Trop2 ECD reveals a complex whereby sacituzumab engages two Trop2 dimers in a 2:4 stoichiometry.

The therapeutic antibody sacituzumab induces trophoblast cell-surface antigen-2 conformational rearrangement.,Ferrao R, Zhang J, Chou CC, Nieto A, Langeslay D, Chatterjee M, Jin D, Hung M, Scott I, Nagel M, Xing W, Letarte S, Wang J, Ambrogelly A, Lansdon EB Structure. 2025 Nov 27:S0969-2126(25)00437-X. doi: 10.1016/j.str.2025.11.002. PMID:41314216<ref>PMID:41314216</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9pi9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ferrao RF]]
[[Category: Lansdon EB]]