title: A theoretical multiscale treatment of protein-protein electron transfer: The ferredoxin/ferredoxin-NADP(+) reductase and flavodoxin/ferredoxin-NADP(+) reductase systems.
abstract: In the photosynthetic electron transfer (ET) chain, two electrons transfer from photosystem I to the flavin-dependent ferredoxin-NADP(+) reductase (FNR) via two sequential independent ferredoxin (Fd) electron carriers. In some algae and cyanobacteria (as Anabaena), under low iron conditions, flavodoxin (Fld) replaces Fd as single electron carrier. Extensive mutational studies have characterized the protein-protein interaction in FNR/Fd and FNR/Fld complexes. Interestingly, even though Fd and Fld share the interaction site on FNR, individual residues on FNR do not participate to the same extent in the interaction with each of the protein partners, pointing to different electron transfer mechanisms. Despite of extensive mutational studies, only FNR/Fd X-ray structures from Anabaena and maize have been solved; structural data for FNR/Fld remains elusive. Here, we present a multiscale modelling approach including coarse-grained and all-atom protein-protein docking, the QM/MM e-Pathway analysis and electronic coupling calculations, allowing for a molecular and electronic comprehensive analysis of the ET process in both complexes. Our results, consistent with experimental mutational data, reveal the ET in FNR/Fd proceeding through a bridge-mediated mechanism in a dominant protein-protein complex, where transfer of the electron is facilitated by Fd loop-residues 40-49. In FNR/Fld, however, we observe a direct transfer between redox cofactors and less complex specificity than in Fd; more than one orientation in the encounter complex can be efficient in ET.
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Jordi Girona 29, E-08034 Barcelona, Spain.
authors.forename: Suwipa
authors.initials: S
authors.lastname: Saen-Oon
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Jordi Girona 29, E-08034 Barcelona, Spain.
authors.forename: Israel
authors.initials: I
authors.lastname: Cabeza de Vaca
authors.affiliation: CONICET, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Padre Jorge Contreras, 1300, Mendoza 5500, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Masone
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Faculty of Sciences, Universidad de Zaragoza, 50009 Zaragoza, Spain; Institute of Biocomputation and Physics of Complex Systems, Universidad de Zaragoza, 50018 Zaragoza Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Medina
authors.affiliation: Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Jordi Girona 29, E-08034 Barcelona, Spain; Institució Catalana de RecercaiEstudis Avançats (ICREA), Passeig Lluís Companys 23, E-08010 Barcelona, Spain. Electronic address: victor.guallar@bsc.es.
authors.forename: Victor
authors.initials: V
authors.lastname: Guallar
mesh_terms: D017033:Anabaena / Q000737:chemistry / Q000201:enzymology; D004579:Electron Transport; D005287:Ferredoxin-NADP Reductase / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D011506:Proteins; D005287:Ferredoxin-NADP Reductase; D009247:NADH, NADPH Oxidoreductases; C116041:flavodoxin NADPH oxidoreductase
keywords: Electronic coupling; FNR/Fd; FNR/Fld; Protein–protein docking; Protein–protein electron transfer; QM/MM e-Pathway