8FBI

Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains

8FBI の概要

• エントリーDOI: 10.2210/pdb8fbi/pdb
• 分子名称: KWOCA_39 (1 entity in total)
• 機能のキーワード: designed protein, protein assemblies, negative design, cryptic transmembrane domains, 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: 33340.49

構造登録者

Wang, J.Y.,Khmelinskaia, A.,Bera, A.K.,King, N.P. (登録日: 2022-11-29, 公開日: 2023-03-22, 最終更新日: 2024-05-22)

主引用文献

Wang, J.Y.J.,Khmelinskaia, A.,Sheffler, W.,Miranda, M.C.,Antanasijevic, A.,Borst, A.J.,Torres, S.V.,Shu, C.,Hsia, Y.,Nattermann, U.,Ellis, D.,Walkey, C.,Ahlrichs, M.,Chan, S.,Kang, A.,Nguyen, H.,Sydeman, C.,Sankaran, B.,Wu, M.,Bera, A.K.,Carter, L.,Fiala, B.,Murphy, M.,Baker, D.,Ward, A.B.,King, N.P.
Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains.
Proc.Natl.Acad.Sci.USA, 120:e2214556120-e2214556120, 2023

PubMed Abstract: Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. The retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the nanoparticles we describe may be broadly useful in biotechnological applications.

PubMed: 36888664
DOI: 10.1073/pnas.2214556120

実験手法

X-RAY DIFFRACTION (3.61 Å)