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Title: De novo design of symmetric ferredoxins that shuttle electrons in vivo

Abstract

A symmetric origin for bacterial ferredoxins was first proposed over 50 y ago, yet, to date, no functional symmetric molecule has been constructed. It is hypothesized that extant proteins have drifted from their symmetric roots via gene duplication followed by mutations. Phylogenetic analyses of extant ferredoxins support the independent evolution of N- and C-terminal sequences, thereby allowing consensus-based design of symmetric 4Fe-4S molecules. All designs bind two [4Fe-4S] clusters and exhibit strongly reducing midpoint potentials ranging from −405 to −515 mV. One of these constructs efficiently shuttles electrons through a designed metabolic pathway in Escherichia coli . These finding establish that ferredoxins consisting of a symmetric core can be used as a platform to design novel electron transfer carriers for in vivo applications. Outer-shell asymmetry increases sequence space without compromising electron transfer functionality.

Authors:
; ; ; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Rice Univ., Houston, TX (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); Gordon and Betty Moore Foundation (GBMF); National Aeronautics and Space Administration (NASA)
OSTI Identifier:
1530618
Alternate Identifier(s):
OSTI ID: 1594002
Grant/Contract Number:  
SC0014462; 80NSSC18M0093
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 116 Journal Issue: 29; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; metalloprotein; ferredoxin; electron transfer; microbiology; consensus design; [4Fe-4S] clusters; bacterial ferredoxin; protein evolution

Citation Formats

Mutter, Andrew C., Tyryshkin, Alexei M., Campbell, Ian J., Poudel, Saroj, Bennett, George N., Silberg, Jonathan J., Nanda, Vikas, and Falkowski, Paul G. De novo design of symmetric ferredoxins that shuttle electrons in vivo. United States: N. p., 2019. Web. doi:10.1073/pnas.1905643116.
Mutter, Andrew C., Tyryshkin, Alexei M., Campbell, Ian J., Poudel, Saroj, Bennett, George N., Silberg, Jonathan J., Nanda, Vikas, & Falkowski, Paul G. De novo design of symmetric ferredoxins that shuttle electrons in vivo. United States. doi:10.1073/pnas.1905643116.
Mutter, Andrew C., Tyryshkin, Alexei M., Campbell, Ian J., Poudel, Saroj, Bennett, George N., Silberg, Jonathan J., Nanda, Vikas, and Falkowski, Paul G. Mon . "De novo design of symmetric ferredoxins that shuttle electrons in vivo". United States. doi:10.1073/pnas.1905643116.
@article{osti_1530618,
title = {De novo design of symmetric ferredoxins that shuttle electrons in vivo},
author = {Mutter, Andrew C. and Tyryshkin, Alexei M. and Campbell, Ian J. and Poudel, Saroj and Bennett, George N. and Silberg, Jonathan J. and Nanda, Vikas and Falkowski, Paul G.},
abstractNote = {A symmetric origin for bacterial ferredoxins was first proposed over 50 y ago, yet, to date, no functional symmetric molecule has been constructed. It is hypothesized that extant proteins have drifted from their symmetric roots via gene duplication followed by mutations. Phylogenetic analyses of extant ferredoxins support the independent evolution of N- and C-terminal sequences, thereby allowing consensus-based design of symmetric 4Fe-4S molecules. All designs bind two [4Fe-4S] clusters and exhibit strongly reducing midpoint potentials ranging from −405 to −515 mV. One of these constructs efficiently shuttles electrons through a designed metabolic pathway in Escherichia coli . These finding establish that ferredoxins consisting of a symmetric core can be used as a platform to design novel electron transfer carriers for in vivo applications. Outer-shell asymmetry increases sequence space without compromising electron transfer functionality.},
doi = {10.1073/pnas.1905643116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 29,
volume = 116,
place = {United States},
year = {2019},
month = {7}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1073/pnas.1905643116

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Cited by: 5 works
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