View source for 9nwr


==Cryo-EM of Class-2 of YM1P nanotube==
<StructureSection load='9nwr' size='340' side='right'caption='[[9nwr]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9nwr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9NWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NWR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1B60:4-(phosphonooxy)[1,1-biphenyl]-4-carboxylic+acid'>A1B60</scene>, <scene name='pdbligand=A1B6Z:dimethyl+D-glutamate'>A1B6Z</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</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=9nwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nwr OCA], [https://pdbe.org/9nwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nwr RCSB], [https://www.ebi.ac.uk/pdbsum/9nwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nwr ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Programmed lytic cell death, including pyroptosis and necroptosis, involves intracellular enzymes that form membrane-rupturing pores. Tumor-associated ectoenzymes such as alkaline phosphatase (ALP), however, offer the potential to initiate lytic death extrinsically. Here, we design a phospho-biphenyl-capped peptide precursor that is selectively dephosphorylated by ALP on cancer cell surfaces, triggering enzyme-instructed peptide self-assembly (EISA) into in situ peptide filaments. These supramolecular filaments physically breach the plasma membrane, overwhelm ESCRT-dependent membrane repair, and induce catastrophic calcium influx, cytoskeletal collapse, and organelle dysfunction. While cryo-EM uncovers 2.5-2.9 A resolution details of ordered dimeric packing that underlies their mechanical rigidity and membrane-rupturing capability, cryo-electron tomography (cryo-ET) reveals the filament penetration of the plasma membrane in live cells. By reprogramming ALP from an immune checkpoint ectoenzyme into a pro-death catalyst, this work establishes a molecular mechanism linking enzymatic catalysis to supramolecular order and membrane failure. More broadly, it outlines a supramolecular chemical-biology framework in which enzyme-triggered assemblies function as programmable executors of cell death.

Cryo-Structural Insights into Enzymatic Peptide Self-Assembly Driving Extrinsic Lytic Cell Death.,Yi M, Guo J, Zia A, Guo W, Tachiyama S, Ashton-Rickardt G, Tan W, Qiao Y, Gong Y, Egelman EH, Liu J, Wang F, Xu B J Am Chem Soc. 2026 Apr 8;148(13):14117-14128. doi: 10.1021/jacs.5c23283. Epub , 2026 Mar 24. PMID:41875418<ref>PMID:41875418</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9nwr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Egelman EH]]
[[Category: Wang F]]
[[Category: Xu B]]
[[Category: Yi M]]
[[Category: Zia A]]