Biology Reference
In-Depth Information
Synechocystis
), cadmium, lead and zinc (AztR in
Anabaena
and CadC in
Staph-
ylococcus aureus
), cadmium and lead (CmtR in
M. tuberculosis
), zinc and cobalt
(CzrA in
S. aureus
), nickel and cobalt (NmtR and KmtR in
M. tuberculosis
)
and copper, silver, zinc and cadmium (BxmR in
Oscillatoria
) (
Osman &
Cavet, 2010
).
One founder member of this family, SmtB, was first cloned and charac-
terized from
Synechococcus
PCC 7942 in 1993. This 122-amino acid protein
functions as a Zn(II)-responsive repressor of a metallothionein involved in
chelating zinc from cytosol (
Huckle et al., 1993
). A few years later, an SmtB
orthologue was described in
Synechocystis
PCC 6803, named ZiaR. This
protein regulates the transcription of an ATPase which exports zinc into
the cytoplasm (
Thelwell et al., 1998
) and it is induced in response to Cd
and excess of Zn (
Houot et al., 2007
). The other founder member, ArsR,
was first described as an As(III)/Sb(III)-responsive repressor in
E. coli
(
Wu
& Rosen, 1991
). In
Synechocystis
PCC 6803, an ArsR orthologue is involved
in arsenic and antimony resistance, and it thus controls the expression of an
operon containing an As(III)/Sb(III)-efflux pump, among other proteins
(
Lopez-Maury, Florencio, & Reyes, 2003
).
More recently, some other SmtB/ArsR proteins have been discovered in
cyanobacteria.
Anabaena
PCC 7120 AztR also represses the transcription of
a zinc efflux pump (
Liu, Golden, & Giedroc, 2005
). A further SmtB/ArsR
family member, AzuR, has been reported but not fully characterized (
Liu
et al., 2008
). Notably, in
Oscillatoria brevis
, the Zn(II)-responsive regulator
BxmR controls the expression of an ATPase and a metallothionein, but
both products are encoded in two physically separate transcription units
(
Liu et al., 2004
). These metal homeostasis systems in
Oscillatoria
remind the
zinc response machinery present in mammalian cells with MTF1, which
also regulates a metallothionein and a Zn-efflux pump (
Jackson, Valentine,
Coneyworth, Mathers, & Ford, 2008
).
3.4.1. Metal-binding sites of SmtB/ArsR family members
The X-ray crystallographic structure of
Synechococcus
apo-SmtB at 2.2 Å
resolution shows this regulator as an elongated dimer consisting of two
monomers related by a twofold axis of symmetry (
Fig. 4.4
). Each mono-
mer contains five α-helices and two β-strands in an ααααββα-fold. Two
of the helices, α3 and α4 (αR), form the standard HTH motif present
in many DNA-binding proteins. SmtB has strong structural similarities to
other HTH transcriptional regulators such as CAP protein or DtxR (
Cook
et al., 1998
).
