Abstract：
:The ubiquitously expressed nitric oxide (NO) receptor soluble guanylate cyclase (sGC) plays a key role in signal transduction. Binding of NO to the N-terminal prosthetic heme moiety of sGC results in approximately 200-fold activation of the enzyme and an increased conversion of GTP into the second messenger cGMP. sGC exists as a heterodimer the dimerization of which is mediated mainly by the central region of the enzyme. In the present work, we constructed deletion mutants within the predicted dimerization region of the sGC alpha(1)- and beta(1)-subunit to precisely map the sequence segments crucial for subunit dimerization. To track mutation-induced alterations of sGC dimerization, we used a bimolecular fluorescence complementation approach that allows visualizing sGC heterodimerization in a noninvasive manner in living cells. Our study suggests that segments spanning amino acids alpha(1)363-372, alpha(1)403-422, alpha(1)440-459, beta(1)212-222, beta(1)304-333, beta(1)344-363, and beta(1)381-400 within the predicted dimerization region are involved in the process of heterodimerization and therefore in the expression of functional sGC.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Rothkegel C,Schmidt PM,Atkins DJ,Hoffmann LS,Schmidt HH,Schröder H,Stasch JPdoi
10.1124/mol.107.036368subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1181-90issue
5eissn
0026-895Xissn
1521-0111pii
mol.107.036368journal_volume
72pub_type
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