MsGC-β3 forms active homodimers and inactive heterodimers with NO-sensitive soluble guanylyl cyclase subunits

David B. Morton, Esther J. Anderson

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Soluble guanylyl cyclases are typically obligate heterodimers, composed of a single alpha and a single beta subunit. MsGC-β3, identified in the tobacco hornworm Manduca sexta, was the first example of a soluble guanylyl cyclase that exhibited enzyme activity without the need for coexpression with additional subunits. Subsequent studies have revealed that the mammalian β2 subunit also shares this property. Using a combination of gel filtration chromatography, coprecipitation and site-directed mutagenesis we show that, as predicted, MsGC-β3 forms active homodimers. We also demonstrate that MsGC-β3 is capable of forming heterodimers with the nitric oxide (NO)-sensitive guanylyl cyclase subunits MsGC-α1 and MsGC-β1. These heterodimers, however, show no enzyme activity and, like mammalian β2 subunits, act in a dominant negative manner when combined with the NO-sensitive subunits to disrupt their activation by NO. In addition, we show that the unique C-terminal domain of MsGC-β3 is not necessary for enzyme activity and might act as an auto-inhibitory domain.

Original languageEnglish (US)
Pages (from-to)937-947
Number of pages11
JournalJournal of Experimental Biology
Volume206
Issue number6
DOIs
StatePublished - Mar 1 2003

Keywords

  • Guanylyl cyclase
  • Manduca sexta
  • Nitric oxide
  • Protein dimerization
  • Tobacco hornworm
  • cGMP

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Molecular Biology
  • Insect Science

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