Disordered Motifs and Domains in Cell Control
Poster Session II
28-POS
Board 4
Characterizing the Function of the Disordered Region in Soluble Guanylyl Cyclase
Candice Benally, Parul Singh,
Matthew Gage
.
Northern Arizona University, Flagstaff, USA.
Signaling by nitric oxide (NO) is a key component in cardiovascular heath as well as links to a
growing number of other diseases such as cancer and diabetes. The primary receptor for NO is
soluble Guanylyl Cyclase (sGC), a heterodimeric protein that is upregulated by binding of NO to
the heme group in the β-subunit. Activation of sGC results in the conversion of GTP to cGMP
and decreased sCG activity is linked to atherosclerosis, aging, loss of memory, acute ischemia,
while increased sGC catalytic activity is associated with endothelial cell proliferation,
vasodilation, cell motility and survival. The activation, catalytic activity and structure of sGC
have been widely studied but the mechanism behind sGC regulation remains poorly understood.
Both subunits of sGC contain four distinct functional domains: an H-NOX, a Per Arnt Sim
(PAS), a coiled-coiled and a C-terminal catalytic domain. Interestingly, N-terminus of the α-
subunit also contains a 70 amino acid intrinsically disordered region (sGC-IDR) with a
previously undetermined function. Using a yeast two-hybrid screen, our lab has identified
putative interactions between sGC-IDR and both an E3 ubiquitin ligase and the muscle protein
titin. These interactions suggest roles for the sGC-IDR in both localization and degradation of
sGC. Experiments are ongoing to characterize the role the sGC-IDR plays in both potential
functions.
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