Requirement for intramolecular domain interaction in activation of G protein alpha subunit by aluminum fluoride and GDP but not by GTP gamma S.
An ion-counterion interaction between the lysine of the NKXD motif in the GTPase domain and an aspartate in the inserted helical domain of alpha subunits of heterotrimeric G proteins, Lys-278 and Asp-158, respectively, of Gs alpha is shown to be essential for activation by AlF4- and partially so for interaction with beta gamma dimers and activation by GTP and receptor. However, this domain interaction is not required for activation by the non-hydrolyzable analog guanosine 5'-3-O-(thio)triphosphate. Proximity of the helical domain to the GTPase domain is thus involved in the fundamental inactive-->active transition of the protein in a way that further distinguishes alpha subunits of heterotrimeric G proteins from ras and ras-like GTPases that lack helical domains and are neither activated by AlF4- nor combine with beta gamma dimers.
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
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Codina
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L
Birnbaumer
D017607:Aluminum Compounds / Q000494:pharmacology*; D000595:Amino Acid Sequence; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006153:Guanosine Diphosphate / Q000494:pharmacology*; D008969:Molecular Sequence Data
D017607:Aluminum Compounds; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride