Molecular handcraft of a well-folded protein chimera.

Autor: Toledo-Patiño S; Max Planck Institute for Developmental Biology, Tübingen, Germany.; Okinawa Institute of Science and Technology Graduate University, Japan., Goetz SK; Max Planck Institute for Developmental Biology, Tübingen, Germany., Shanmugaratnam S; Max Planck Institute for Developmental Biology, Tübingen, Germany.; Department of Biochemistry, University of Bayreuth, Germany., Höcker B; Max Planck Institute for Developmental Biology, Tübingen, Germany.; Department of Biochemistry, University of Bayreuth, Germany., Farías-Rico JA; Max Planck Institute for Developmental Biology, Tübingen, Germany.; Synthetic Biology Program, Center for Genome Sciences, National Autonomous University of Mexico, Cuernavaca, Mexico.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2024 Jun; Vol. 598 (11), pp. 1375-1386. Date of Electronic Publication: 2024 Mar 20.
DOI: 10.1002/1873-3468.14856
Abstrakt: Modular assembly is a compelling pathway to create new proteins, a concept supported by protein engineering and millennia of evolution. Natural evolution provided a repository of building blocks, known as domains, which trace back to even shorter segments that underwent numerous 'copy-paste' processes culminating in the scaffolds we see today. Utilizing the subdomain-database Fuzzle, we constructed a fold-chimera by integrating a flavodoxin-like fragment into a periplasmic binding protein. This chimera is well-folded and a crystal structure reveals stable interfaces between the fragments. These findings demonstrate the adaptability of α/β-proteins and offer a stepping stone for optimization. By emphasizing the practicality of fragment databases, our work pioneers new pathways in protein engineering. Ultimately, the results substantiate the conjecture that periplasmic binding proteins originated from a flavodoxin-like ancestor.
(© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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