Dimerization region of soluble guanylate cyclase characterized by bimolecular fluorescence complementation in vivo

Christiane Rothkegel, Peter M. Schmidt, Derek John Atkins, Linda Sarah Hoffmann, Harald H.H.W. Schmidt, Henning Schröder, Johannes Peter Stasch

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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 ∼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 α1- and β1-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 α1363-372, α1403-422, α1440- 459, β1212-222, β1304-333, β 1344-363, and β1381-400 within the predicted dimerization region are involved in the process of heterodimerization and therefore in the expression of functional sGC.

Original languageEnglish (US)
Pages (from-to)1181-1190
Number of pages10
JournalMolecular Pharmacology
Volume72
Issue number5
DOIs
StatePublished - Nov 1 2007

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