Evolution and cellular function of monothiol glutaredoxins: involvement
in iron-sulphur cluster assembly
Felipe Vilella 1, Rui Alves 1, María Teresa
Rodríguez-Manzaneque 1, Gemma Bellí 1,
Swarna Swaminathan 2, Per Sunnerhagen 2, Enrique Herrero
1
1Departament de Ciències Mèdiques Bàsiques,
Facultat de Medicina, Universitat de Lleida, Rovira Roure 44, 25198-Lleida,
Spain
2Department of Cell and Molecular Biology, Göteborg University,
PO Box 462, S-40530 Göteborg, Sweden
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.