title: Evolution and cellular function of monothiol glutaredoxins: involvement in iron-sulphur cluster assembly.
abstract: A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron-sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron-sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary co-occurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Rovira Roure 44, Lleida 25198, Spain.
authors.forename: Felipe
authors.initials: F
authors.lastname: Vilella
authors.forename: Rui
authors.initials: R
authors.lastname: Alves
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Rodríguez-Manzaneque
authors.forename: Gemma
authors.initials: G
authors.lastname: Bellí
authors.forename: Swarna
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero