De novo design of symmetric ferredoxins that shuttle electrons in vivo

Mutter, Andrew C.; Tyryshkin, Alexei M.; Campbell, Ian J.; Poudel, Saroj; Bennett, George N.; Silberg, Jonathan J.; Nanda, Vikas; Falkowski, Paul G.

doi:10.1073/pnas.1905643116

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

Journal Article · 03 July 2019 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.1905643116 · OSTI ID:1530618

Mutter, Andrew C. ^[1]; Tyryshkin, Alexei M. ^[1]; Campbell, Ian J. ^[2]; Poudel, Saroj ^[3]; Bennett, George N. ^[2]; Silberg, Jonathan J. ^[2];

^[4]; Falkowski, Paul G. ^[1]

Rutgers Univ., New Brunswick, NJ (United States)
Rice Univ., Houston, TX (United States)
Rutgers Univ., New Brunswick, NJ (United States). Inst. of Earth, Ocean, and Atmospheric Sciences
Rutgers Univ., Piscataway, NJ (United States). Center for Advanced Biotechnology and Medicine

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.

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Research Organization:: Rice Univ., Houston, TX (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); Gordon and Betty Moore Foundation (GBMF); National Aeronautics and Space Administration (NASA)

Grant/Contract Number:: SC0014462; 80NSSC18M0093

OSTI ID:: 1530618

Alternate ID(s):: OSTI ID: 1594002

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 29; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 33 works

Citation information provided by
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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
metalloprotein
ferredoxin
electron transfer
microbiology
consensus design
[4Fe-4S] clusters
bacterial ferredoxin
protein evolution