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==== | ==Crystal structure of Tspan15 large extracellular loop (Tspan15 LEL) in complex with 1C12 Fab== | ||
<StructureSection load='7rd5' size='340' side='right'caption='[[7rd5]]' scene=''> | <StructureSection load='7rd5' size='340' side='right'caption='[[7rd5]], [[Resolution|resolution]] 3.60Å' 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'>[[7rd5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RD5 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=7rd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rd5 OCA], [https://pdbe.org/7rd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rd5 RCSB], [https://www.ebi.ac.uk/pdbsum/7rd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rd5 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]] 3.6Å</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=7rd5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rd5 OCA], [https://pdbe.org/7rd5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rd5 RCSB], [https://www.ebi.ac.uk/pdbsum/7rd5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rd5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TSN15_HUMAN TSN15_HUMAN] Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:26686862, PubMed:30463011). Promotes ADAM10-mediated cleavage of CDH2 (By similarity). Negatively regulates ligand-induced Notch activity probably by regulating ADAM10 activity (PubMed:26686862).[UniProtKB:F7BWT7]<ref>PMID:26686862</ref> <ref>PMID:30463011</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Tetraspanins are four-pass transmembrane proteins that function by regulating trafficking of partner proteins and organizing signaling complexes in the membrane. Tspan15, one of a six-member TspanC8 subfamily, forms a complex that regulates the trafficking, maturation, and substrate selectivity of the transmembrane protease ADAM10, an essential enzyme in mammalian physiology that cleaves a wide variety of membrane-anchored substrates, including Notch receptors, amyloid precursor protein, cadherins, and growth factors. We present here crystal structures of the Tspan15 large extracellular loop (LEL) required for functional association with ADAM10 both in isolation and in complex with the Fab fragment of an anti-Tspan15 antibody. Comparison of the Tspan15 LEL with other tetraspanin LEL structures shows that a core helical framework buttresses a variable region that structurally diverges among LELs. Using co-immunoprecipitation and a cellular N-cadherin cleavage assay, we identify a site on Tspan15 required for both ADAM10 binding and promoting substrate cleavage. | |||
Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 binding site.,Lipper CH, Gabriel KH, Seegar TCM, Durr KL, Tomlinson MG, Blacklow SC Structure. 2021 Nov 2. pii: S0969-2126(21)00375-0. doi:, 10.1016/j.str.2021.10.007. PMID:34739841<ref>PMID:34739841</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rd5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Blacklow SC]] | |||
[[Category: Durr KL]] | |||
[[Category: Gabriel KH]] | |||
[[Category: Lipper CH]] | |||
[[Category: Seegar TCM]] | |||
[[Category: Tomlinson MG]] | |||
Latest revision as of 19:29, 18 October 2023
Crystal structure of Tspan15 large extracellular loop (Tspan15 LEL) in complex with 1C12 FabCrystal structure of Tspan15 large extracellular loop (Tspan15 LEL) in complex with 1C12 Fab
Structural highlights
FunctionTSN15_HUMAN Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:26686862, PubMed:30463011). Promotes ADAM10-mediated cleavage of CDH2 (By similarity). Negatively regulates ligand-induced Notch activity probably by regulating ADAM10 activity (PubMed:26686862).[UniProtKB:F7BWT7][1] [2] Publication Abstract from PubMedTetraspanins are four-pass transmembrane proteins that function by regulating trafficking of partner proteins and organizing signaling complexes in the membrane. Tspan15, one of a six-member TspanC8 subfamily, forms a complex that regulates the trafficking, maturation, and substrate selectivity of the transmembrane protease ADAM10, an essential enzyme in mammalian physiology that cleaves a wide variety of membrane-anchored substrates, including Notch receptors, amyloid precursor protein, cadherins, and growth factors. We present here crystal structures of the Tspan15 large extracellular loop (LEL) required for functional association with ADAM10 both in isolation and in complex with the Fab fragment of an anti-Tspan15 antibody. Comparison of the Tspan15 LEL with other tetraspanin LEL structures shows that a core helical framework buttresses a variable region that structurally diverges among LELs. Using co-immunoprecipitation and a cellular N-cadherin cleavage assay, we identify a site on Tspan15 required for both ADAM10 binding and promoting substrate cleavage. Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 binding site.,Lipper CH, Gabriel KH, Seegar TCM, Durr KL, Tomlinson MG, Blacklow SC Structure. 2021 Nov 2. pii: S0969-2126(21)00375-0. doi:, 10.1016/j.str.2021.10.007. PMID:34739841[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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