Adenylyl Cyclase Type II Domains Involved in G St
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- 作者：Silke Weitmann ; Gü ; nter Schultz ; and Christiane Kleuss
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：September 11, 2001
- 年：2001
- 卷：40
- 期：36
- 页码：10853 - 10858
- 全文大小：152K
- 年卷期：v.40,no.36(September 11, 2001)
- ISSN：1520-4995
文摘
Mammalian particulate adenylyl cyclases contain two transmembrane regions (M1 and M2)and two cytosolic domains (C1 and C2) forming the catalytic core. The cytosolic domains are subdividedinto a highly conserved region (part a) and a region with lower similarity (part b). Hypothetical modelsexist that account for the mechanism by which G
s and forskolin stimulate mammalian adenylyl cyclase.In contrast, little is known about how G
dimers regulate catalysis. The so-called QEHA region locatedin the C2a domain of type II adenylyl cyclase has been proposed to represent a site of interaction. Herewe show (i) that the QEHA region directly interacts with G but (ii) that it is of minor importance forthe stimulation of type II adenylyl cyclase because it can be replaced by corresponding, nonidenticalregions of other adenylyl cyclase isoforms without altering the stimulatory effect of G and (iii) that theC1b region is necessary for G to exert a stimulatory effect on adenylyl cyclase type II as in a C1bdeletion mutant the G regulation was specifically impeded whereas the Gs- and forskolin-mediatedstimulation was maintained.
s and forskolin stimulate mammalian adenylyl cyclase.In contrast, little is known about how G dimers regulate catalysis. The so-called QEHA region locatedin the C2a domain of type II adenylyl cyclase has been proposed to represent a site of interaction. Herewe show (i) that the QEHA region directly interacts with G but (ii) that it is of minor importance forthe stimulation of type II adenylyl cyclase because it can be replaced by corresponding, nonidenticalregions of other adenylyl cyclase isoforms without altering the stimulatory effect of G and (iii) that theC1b region is necessary for G to exert a stimulatory effect on adenylyl cyclase type II as in a C1bdeletion mutant the G regulation was specifically impeded whereas the Gs- and forskolin-mediatedstimulation was maintained.