Biology Reference
In-Depth Information
5. PROPOSED FUNCTIONS FOR THE 2/2Hb FAMILY
Although the number of the deposited 2/2Hb sequences has grown
rapidly over the past years, limited functional information is currently avail-
able for these proteins. Examples of proposed functions, consistent with
observed biophysical properties, include nitric oxide detoxification, protec-
tion from reactive oxygen and nitrogen species, dioxygen scavenging, and
recently sulphide binding (
Hill et al., 1996; Nicoletti et al., 2010; Ouellet
et al., 2002; Parrilli et al., 2010; Scott et al., 2010; Vinogradov & Moens,
2008
). However, the diversity of physiological and environmental contexts
in which 2/2Hbs are found suggests that additional enzymatic activities and
insights into haem chemistry are yet to be discovered. For example, group
I 2/2HbN of the unicellular green alga
C. eugametos
is induced in response to
active photosynthesis and is localized partly along the chloroplast thylakoid
membranes (
Couture & Guertin, 1996
). Group I 2/2HbN from the ciliated
protozoa
P. caudatum
may supply O
2
to the mitochondria (
Wittenberg et al.,
2002
). Moreover, group I 2/2HbN from the
Nostoc
sp. cyanobacterium is
thought to protect the nitrogen-fixation apparatus from oxidative damage
through O
2
scavenging (
Hill et al., 1996
).
Most of the functional analyses have been reported for 2/2Hbs from
mycobacterial species, in particular, group I 2/2HbN in
M. tuberculosis
,
M. bovis
,
M. smegmatis,
and
M. avium
, group II 2/2HbO in
M. leprae
and
all the above species, while group III 2/2HbP in
M. avium
only
(
Vinogradov et al., 2006; Vuletich & Lecomte, 2006; Wittenberg et al.,
2002
). The regression in content of 2/2Hb paralogues from
M. avium
(three
2/2Hbs), through
M. tuberculosis
(two 2/2Hbs), to
M. leprae
(one 2/2Hb) has
been proposed to reflect an adaptation from saprophytic lifestyle to obligate
intracellular parasitism, which paralleled the loss of functions provided by
2/2HbN and 2/2HbP. These results are consistent with the general notion
that a 2/2HbO-like globin provided the ancestor structure from which
2/2HbNs and 2/2HbPs, as well as the classical 3-on-3 structural fold,
originated (
Nakajima,
ยด
lvarez-Salgado, Kikuchi, & Arredondo-Peter,
2005; Vinogradov et al., 2006; Vuletich & Lecomte, 2006
).
Mycobacterial 2/2Hbs have been mostly implicated in scavenging of
reactive nitrogen species. During infection, mycobacteria have to face the
toxic effects of reactive nitrogen species, primarily NO, produced by acti-
vated macrophages expressing inducible NO synthase (
Cooper, Adams,
Dalton, Appelberg, & Ehlers, 2002; MacMicking et al., 1997; Nathan &
