trans

CYCLIC NUCLEOTIDES 257
The structure and activity of
mammalian adenylyl and
guanylyl cyclases
Nine different mammalian adenylyl cyclase
(AC) cell-surface isoforms and one soluble
isoform have now been characterized, each
of which has a distinct tissue distribution
and regulatory specificity. All membrane
forms conform to the same basic structure
(Figure 11.4A); they consist of two catalytic
pseuodsymmetrical domains (C1 and C2)
separated by six transmembrane helices, with
a further six transmembrane helices located
towards the amino terminus. The two catalytic
domains dimerize to form the active enzyme.
Mammalian ACs have no known receptor
capability. Instead the activating ligand binds
to a G-protein-coupled receptor, leading to
the dissociation of the G from the G subunits
in the associated heterotrimeric G-protein complex.
The binding of either G or G results in
the activation or inhibition of AC depending
on the AC and G protein isoforms involved
(Figure 11.4A). It has been estimated that each
receptor may activate up to 100 heterotrimeric
G-protein molecules.
In mammalian cells, cAMP has a major role
in controlling gene expression and metabolism.
One of the major signal transduction pathways
involves the binding of cAMP to the regulatory
subunits of specific cAMP-dependent
protein kinases (PKA). This causes dissociation
FIGURE 11.4
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BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA