8GL3

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

8GL3 の概要

• エントリーDOI: 10.2210/pdb8gl3/pdb
• 分子名称: pRLB-519 (2 entities in total)
• 機能のキーワード: protein design, ph-responsive, membrane lysis, de novo protein
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27599.22

構造登録者

Goldbach, N.,Bera, A.K.,Baker, D.,Kang, A. (登録日: 2023-03-20, 公開日: 2023-09-06, 最終更新日: 2023-11-08)

主引用文献

Goldbach, N.,Benna, I.,Wicky, B.I.M.,Croft, J.T.,Carter, L.,Bera, A.K.,Nguyen, H.,Kang, A.,Sankaran, B.,Yang, E.C.,Lee, K.K.,Baker, D.
De novo design of monomeric helical bundles for pH-controlled membrane lysis.
Protein Sci., 32:e4769-e4769, 2023

PubMed Abstract: 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 the 30 designs that were experimentally tested, all expressed in Escherichia 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.

PubMed: 37632837
DOI: 10.1002/pro.4769

実験手法

X-RAY DIFFRACTION (2.3 Å)