| Autor: |
Goverde CA, Pacesa M, Goldbach N, Dornfeld LJ, Balbi PEM, Georgeon S, Rosset S, Kapoor S, Choudhury J, Dauparas J, Schellhaas C, Kozlov S, Baker D, Ovchinnikov S, Vecchio AJ, Correia BE |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 07. Date of Electronic Publication: 2024 Mar 07. |
| DOI: |
10.1101/2023.05.09.540044 |
| Abstrakt: |
De novo design of complex protein folds using solely computational means remains a significant challenge. Here, we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from GPCRs, are not found in the soluble proteome and we demonstrate that their structural features can be recapitulated in solution. Biophysical analyses reveal high thermal stability of the designs and experimental structures show remarkable design accuracy. The soluble analogues were functionalized with native structural motifs, standing as a proof-of-concept for bringing membrane protein functions to the soluble proteome, potentially enabling new approaches in drug discovery. In summary, we designed complex protein topologies and enriched them with functionalities from membrane proteins, with high experimental success rates, leading to a de facto expansion of the functional soluble fold space. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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