An expandable, modular de novo protein platform for precision redox engineering.
bioenergetics
heme proteins
protein design
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
medline:
26
7
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
The electron-conducting circuitry of life represents an as-yet untapped resource of exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure of a de novo diheme "maquette" protein, 4D2, which we subsequently use to create an expanded, modular platform for heme protein design. A well-folded monoheme variant was created by computational redesign, which was then utilized for the experimental validation of continuum electrostatic redox potential calculations. This demonstrates how fundamental biophysical properties can be predicted and fine-tuned. 4D2 was then extended into a tetraheme helical bundle, representing a 7 nm molecular wire. Despite a molecular weight of only 24 kDa, electron cryomicroscopy illustrated a remarkable level of detail, indicating the positioning of the secondary structure and the heme cofactors. This robust, expressible, highly thermostable and readily designable modular platform presents a valuable resource for redox protein design and the future construction of artificial electron-conducting circuitry.
Identifiants
pubmed: 37487099
doi: 10.1073/pnas.2306046120
pmc: PMC10400981
doi:
Substances chimiques
Hemeproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2306046120Subventions
Organisme : European Research Council
ID : 101021207
Pays : International
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M009122/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210701/Z/18/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T008741/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R016445/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202804/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBW003449/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206181/Z/17/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M02315X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L01386X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R000484/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M025624/1
Pays : United Kingdom
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