<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins
homologous to the <italic>Saccharomyces cerevisiae</italic> 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 <italic>in vivo</italic> interaction between Grx5 and Isa1. Sequence comparison techniques and
cladistics indicate that the other two monothiol glutaredoxins of <italic>S. cerevisiae</italic>, 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.</p>
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Comp Funct Genomics. 2004 Jun; 5(4):328-341