The NH2-terminal α subunit attenuator domain confers regulation of G protein activation by βγ complexes
✍ Scribed by N. Dhanasekaran; Shoji Osawa; Gary L. Johnson
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- English
- Weight
- 662 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
G, and G,, respectively, activate and inhibit the enzyme adenylyl cyclase. Regulation of adenylyl cycldse by the heterotrimeric G, and G, proteins requires the dissociation of GDP and binding of GTP to the a, or a, subunit. The 0-y subunit complex of G, and G, functions, in part, to inhibit GDP dissociation and a subunit activation by GTP. Multiple p and y polypeptides are expressed in different cell types, but the functional significance for this heterogeneity is unclear. The P-y complex from retinal rod outer segments (Py,) has been shown to discriminate between a, and a, subunits (Helman et al: Eur J Biochem 169: [431][432][433][434][435][436][437][438][439] 1987). Py, efficiently interacts with a,-like G protein subunits, but poorly recognizes the a, subunit. P-y, was, therefore, used to define regions of the a, subunit polypeptide that conferred selective regulation compared to the a, polypeptide. A series of a subunit chimeras having NH,-terminal a, and COOH-terminal a, sequences were characterized for their regulation by Py,, measured by the kinetics of GTf'yS activation of adenylyl cyclase. A 122 amino acid NH,-terminal region of the a, polypeptide encoded within an aia, chimera was sufficient for Py, to discriminate the chimera from as. A shorter 54 amino acid a, sequence substituted for the corresponding NH,-terminal region of a, was insufficient to support the a,-like interaction with Py,. The findings are consistent with our previous observation (Osawa et al: Cell 63:697-706,1990) that a region in the NH,-terminal moiety functions as an attenuator domain controlling GDP dissociation and GTP activation of the a subunit polypeptide m d that the attenuator domain is involved in functional recognition and regulation by Py complexes.