View source for 8gl3


==De novo design of monomeric helical bundles for pH-controlled membrane lysis==
<StructureSection load='8gl3' size='340' side='right'caption='[[8gl3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gl3]] is a 1 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=8GL3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GL3 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]] 2.3&#8491;</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=8gl3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gl3 OCA], [https://pdbe.org/8gl3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gl3 RCSB], [https://www.ebi.ac.uk/pdbsum/8gl3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gl3 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Targeted intracellular delivery via receptor-mediated endocytosis requires the delivered cargo to escape the endosome to prevent lysosomal degradation. This can in principle be achieved by membrane lysis tightly restricted to endosomal membranes upon internalization to avoid general membrane insertion and lysis. Here we describe the design of small monomeric proteins with buried histidine containing pH-responsive hydrogen bond networks and membrane permeating amphipathic helices. Of 30 designs that were experimentally tested, all expressed in E. coli, 13 were monomeric with the expected secondary structure, and 4 designs disrupted artificial liposomes in a pH-dependent manner. Mutational analysis showed that the buried histidine hydrogen bond networks mediate pH-responsiveness and control lysis of model membranes within a very narrow range of pH (6.0 - 5.5) with almost no lysis occurring at neutral pH. These tightly controlled lytic monomers could help mediate endosomal escape in designed targeted delivery platforms. This article is protected by copyright. All rights reserved.

De novo design of monomeric helical bundles for pH-controlled membrane lysis.,Goldbach N, Benna I, Wicky BIM, Croft JT, Carter L, Bera AK, Nguyen H, Kang A, Sankaran B, Yang EC, Lee KK, Baker D Protein Sci. 2023 Aug 26:e4769. doi: 10.1002/pro.4769. PMID:37632837<ref>PMID:37632837</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Baker D]]
[[Category: Bera AK]]
[[Category: Goldbach N]]
[[Category: Kang A]]