title: Cellular Assays for Ferredoxins: A Strategy for Understanding Electron Flow through Protein Carriers That Link Metabolic Pathways.
abstract: The ferredoxin (Fd) protein family is a structurally diverse group of iron-sulfur proteins that function as electron carriers, linking biochemical pathways important for energy transduction, nutrient assimilation, and primary metabolism. While considerable biochemical information about individual Fd protein electron carriers and their reactions has been acquired, we cannot yet anticipate the proportion of electrons shuttled between different Fd-partner proteins within cells using biochemical parameters that govern electron flow, such as holo-Fd concentration, midpoint potential (driving force), molecular interactions (affinity and kinetics), conformational changes (allostery), and off-pathway electron leakage (chemical oxidation). Herein, we describe functional and structural gaps in our Fd knowledge within the context of a sequence similarity network and phylogenetic tree, and we propose a strategy for improving our understanding of Fd sequence-function relationships. We suggest comparing the functions of divergent Fds within cells whose growth, or other measurable output, requires electron transfer between defined electron donor and acceptor proteins. By comparing Fd-mediated electron transfer with biochemical parameters that govern electron flow, we posit that models that anticipate energy flow across Fd interactomes can be built. This approach is expected to transform our ability to anticipate Fd control over electron flow in cellular settings, an obstacle to the construction of synthetic electron transfer pathways and rational optimization of existing energy-conserving pathways.
authors.affiliation: Systems, Synthetic, and Physical Biology Graduate Program, Rice University , MS-180, 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Atkinson
authors.affiliation: Biochemistry and Cell Biology Graduate Program, Rice University , MS-140, 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Campbell
authors.affiliation: Department of Biosciences, Rice University , MS-140, 6100 Main Street, Houston, Texas 77005, United States.|Department of Chemical and Biomolecular Engineering, Rice University , MS-362, 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: George N
authors.initials: GN
authors.lastname: Bennett
authors.affiliation: Department of Biosciences, Rice University , MS-140, 6100 Main Street, Houston, Texas 77005, United States.|Department of Bioengineering, Rice University , MS-142, 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Jonathan J
authors.identifier: http://orcid.org/0000-0001-5612-0667
authors.initials: JJ
authors.lastname: Silberg
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000166:cytology / Q000378:metabolism*; D004579:Electron Transport; D004583:Electrons; D005288:Ferredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D005288:Ferredoxins; D007506:Iron-Sulfur Proteins