Biomedical Engineering Reference
In-Depth Information
Fig. 8.8
Comparison of the structures of the phosducin-Gb g and Gb
5
-RGS9 complexes.
Phosducin binds the same face of Gb
1
as does the N-terminal DEP/DHEX domain of RGS9 on
Gb
5
. This steric hindrance blocks PhLP1 from binding to the Gb
5
-RGS dimer. The color code of
the proteins is: phosducin -
teal
, G b
1
-
blue
, G g -
red
, G b
5
-
dark blue
, RGS DEP/DHEX domain
-
pink
, RGS Gg-like domain -
dark red
, RGS domain -
orange
. PDB numbers for the structures
are: phosducin-Gb g (1A0R) (Gaudet et al.
1996
) and G b
5
-RGS9 (2PBI) (Cheever et al.
2008
)
intermediate (Howlett et al.
2009
). The nascent RGS protein may be delivered to
Gb
5
on CCT by the Hsc70 chaperone given that Hsc70 is known to deliver folding
clients to CCT (Cuellar et al.
2008
) and an interaction between Hsc70 and RGS7 as
been reported previously (Posokhova et al.
2010
) . Once the G b
5
-RGS7 dimer is
formed on CCT, it can then be released to interact with its membrane anchoring
protein. Only then is the complex fully stabilized and able to carry out its function
in accelerating GTP hydrolysis on Ga subunits (Gospe et al.
2011
) .
8.6
Future Directions
Research over the past decade has yielded considerable insight into the mecha-
nism of assembly of the obligate dimers of Gb subunits with Gg subunits and RGS
proteins. The data point to PhLP1 as an important co-chaperone with CCT in the
folding and assembly of all complexes containing Gb subunits. Yet there are many
Fig. 8.7
(continued) using the pulse-chase assay as in Panel a. The data are from three separate
experiments. A CCTz immunoblot showing the degree of siRNA knockdown is shown below the
graph. In Panel d, HEK-293 T cells were treated with siRNA to CCTz or Lamin A/C control and
the rate of Gb
1
g
2
dimer assembly was measured using the pulse-chase assay as in Panel a. The
data are from three separate experiments. (The Figure was reproduced from reference (Howlett
et al.
2009
) )
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