Biology Reference
In-Depth Information
bacterium that results in the upregulation of over 125 genes. Three proteins,
RsbR, RsbS, and RsbT, constitute the stressosome complex that presents a
pseudo-icosahedral core with sensory extensions provided by the
N-terminal domain of RsbR (
Chen et al., 2003
). As such, RsbR comprises
an N-terminal sensor domain and a C-terminal STAS domain that interacts
with the RNAP
s
B
subunit inducing gene transcription.
In 2005, Murray and colleagues published the crystal structure of the
RsbR N-terminal domain (N-RsbR). Unexpectedly, N-RsbR displays
the classical globin fold architecture, though lacking helices C and D as many
known haem-binding globins do (
Murray, Delumeau, & Lewis, 2005
). The
HemAT globin domain was found to be the structural match for N-RsbR
and the relative protein sequence alignment revealed 13.5% of identity.
Intriguingly, of the universally conserved residues in globins, none is present
in RsbR, including the proximal histidine (replaced by an alanine). Again,
the putative haem-pocket space is occupied by the helices E and F, brought
much closer together than in known globins (
Murray et al., 2005
).
The signal transduction from the N- to the C-terminal domain is
suggested to be mediated by a conserved 13-residue linker region. As
N-RsbR is homo-dimeric in the soluble and in the crystallized forms
(
Murray et al., 2005
), the two corresponding linker regions are also close
together and interact via a conserved interface (
Marles-Wright et al.,
2008
). Mutations introduced in the linker region at the conserved positions
in order to disrupt its dimerization capability, thought to inactivate the
stressosome, resulted in 30-fold increased stress-mediated response in
unstressed cells. On the other hand, mutations in the non-conserved posi-
tions decreased the output in stressed and non-stressed cells (
Gaidenko, Bie,
Baldwin, & Price, 2012
). These findings confirm the involvement of the
linker region in the stressosome outcome, but weaken the hypothesis that
the non-haem globin domain is responsible for stress signal sensing. There-
fore, another hypothesis is that the N-terminal non-haem globin domain
serves only as a steady-state regulator of the stressosome, and that the real
stress sensor is somewhere downstream of the protein sequence. It is clear
that a non-conventional signal transduction, yet to be characterized, is pre-
sent (
Gaidenko et al., 2012
).
Some important aspects still remain to be unravelled. We do not know
yet whether this non-haem globin domain is the functional form, as a weakly
bound cofactor might be lost during purification. In parallel, evidence is
available neither on how the stress signal is sensed nor on how it is commu-
nicated to the stressosome.
