8gl3

De novo design of monomeric helical bundles for pH-controlled membrane lysis

spinqualitylabelsall models 8gl3, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8gl3 is a 1 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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