Biology Reference
In-Depth Information
ensure the activation of
Rr
CooA only when CO intracellular concentration
occurs at a high (
m
M) level for sufficiently long time (longer than 1 min), and
the activation is efficient over a narrow range of CO concentrations (
Puranik
et al., 2004
).
As expected, the CO-binding kinetics is influenced by the presence of
the DNA-binding domain and, even more, when DNA is bound. It has
been proposed that the second domain helps to form a hydrophobic trap
for CO, whereas the DNA binding rigidifies the whole structure, thus opti-
mizing the CO-dependent signal (
Benabbas, Karunakaran, Youn, Poulos, &
Champion, 2012
).
A
Rr
CooA homologue (29% identity) has been identified in the thermo-
philic CO-oxidizing bacterium named
Carboxydothermus hydrogenoformans
(
Ch
CooA) (
Inagaki et al., 2005
), which is activated, next to CO, also upon
NO binding (
Clark et al., 2006
). This unexpected activation is explained by
the formation of a six-coordinated Fe(II)-NO adduct, where in
Rr
CooA,
NO forms a five-coordinated form (
Clark et al., 2006; Reynolds
et al., 2000
).
The crystal structure of
Ch
CooA bound to exogenous imidazole is
known and provides further atomic-resolution information on the molec-
ular mechanisms that drive ligand-binding-dependent activation (
Komori,
Inagaki, Yoshioka, Aono, & Higuchi, 2007
). Upon CO binding, the
N-terminal region is displaced and bends, creating a bridge between the
two major domains. This rearrangement determines structural modifications
in the D-helix, which cause the movement of the DNA-binding domains
(
Fig. 1.3
B). The DNA-binding domains slide closer to the effector-binding
domains, thus exposing the F-helix for unambiguous DNA-recognition
(
Borjigin et al., 2007
).
2.2.1.2 The neuronal PAS domain protein 2
The NPAS2 is a dimeric mammalian transcription factor mainly expressed in
the forebrain under the control of the retinoic acid-related orphan receptor y
(
Hogenesch et al., 1998; Takeda, Kang, Angers, & Jetten, 2011; Zhou et al.,
1997
). It is known that the NPAS2 transcription function is strongly
inhibited upon CO binding (
Uchida et al., 2005
).
Evidence shows that NPAS2 interacts with the brain and muscle Arnt-
like protein 1 transcription factor (BMAL1) and, as such, functions as a
hetero-dimer (
Reick et al., 2001
). NPAS2:BMAL1, in particular, is
involved in the expression of genes of the circadian rhythm (
Dudley
et al., 2003; Rutter, Reick, Wu, & McKnight, 2001
), and the activation