Biology Reference
In-Depth Information
Prochlorococcus
strains, such as SS120 or MED4, harbouring the smallest cya-
nobacterial genomes contain only two
fur
genes, in contrast with
Acaryochlo-
ris marina
MBIC11017 that exhibits the highest number of Fur and Fur-like
paralogues, namely five Fur-like, four PerR-like and four Zur-like members
(
Table 4.1
)
.
This scenario suggests that this family of transcriptional regula-
tors presents a functional specialization in cyanobacteria though microar-
ray-based analysis has also evidenced redundant functions and cross-talking
between Fur proteins.
3.1.2.1. FurA and their orthologues
Biochemical and genetic studies aimed at discovering the functions of
the three members of the family identified in
Anabaena
(
Nostoc
) PCC
7120, namely FurA, FurB and FurC (
Hernández, López-Gomollón et al.,
2004
), showed that FurA, the
all1691
gene product, is the most abundant
of the three proteins under standard culture conditions. FurA is a master
regulator acting as a hub that connects iron homeostasis, oxidative stress
defence and other relevant metabolic pathways (
Fillat, 2010
). In
Anabaena
,
FurA seems both to act as the ferric uptake regulator and to perform the
PerR functions. Unlike the other two Fur paralogues, FurA is an essential
protein under standard culture conditions (
González, Bes, Barja, Peleato,
& Fillat, 2010
;
Hernández, Muro-Pastor et al., 2006
).
Anabaena
mutants
overexpressing FurA have lower iron content than the WT strain and an
iron-deficient phenotype (
González et al., 2010
;
Hernández et al., 2010
).
Because of the tight connection between iron metabolism and oxidative
stress, the fact that the same protein may respond to both signals would
allow a more efficient co-ordination between iron uptake and storage and
the redox status of the cell. Since the current working model for FurA
is based on the repression of target genes using Fe
2+
as co-repressor, a
dual-sensing mechanism could rely on iron oxidation produced by oxida-
tive damage that, in turn, would lead to the dissociation of Fur from the
DNA, thus allowing the transcription of genes involved in ROS quenching
(
Fig. 4.3
). Single-molecule assays show the tendency of FurA to form tri-
mers and higher aggregates via disulphide bridges in the presence of H
2
O
2
(
Lostao, Peleato, Gomez-Moreno, & Fillat, 2010
), suggesting that oxida-
tive injury could irreversibly produce nonfunctional dimers, activating the
concerted response to oxidative stress.
Similar to
Anabaena
PCC 7120, the genome of
Synechocystis
PCC 6803
contains three
fur
paralogues. As in the case of
furA
, attemps to inactivate the
sll0567
gene resulted in partially segregated mutants (
Kunert, Vinnemeier,
