{"doi":"10.1002/jcb.240470409","title":"The NH<sub>2</sub>‐terminal α subunit attenuator domain confers regulation of G protein activation by βγ complexes","abstract":"<jats:title>Abstract</jats:title><jats:p>G<jats:sub>s</jats:sub> and G<jats:sub>i</jats:sub>, respectively, activate and inhibit the enzyme adenylyl cyclase. Regulation of adenylyl cyclase by the heterotrimeric G<jats:sub>s</jats:sub> and G<jats:sub>i</jats:sub> proteins requires the dissociation of GDP and binding of GTP to the α<jats:sub>s</jats:sub> or α<jats:sub>i</jats:sub> subunit. The βγ subunit complex of G<jats:sub>s</jats:sub> and G<jats:sub>i</jats:sub> functions, in part, to inhibit GDP dissociation and α subunit activation by GTP. Multiple β and γ polypeptides are expressed in different cell types, but the functional significance for this heterogeneity is unclear. The βγ complex from retinal rod outer segments (βγ<jats:sub>t</jats:sub>) has been shown to discriminate between α<jats:sub>i</jats:sub> and α<jats:sub>s</jats:sub> subunits (Helman et al: Eur J Biochem 169:431–439, 1987). βγ<jats:sub>t</jats:sub> efficiently interacts with α<jats:sub>i</jats:sub>‐like G protein subunits, but poorly recognizes the α<jats:sub>s</jats:sub> subunit. βγ<jats:sub>t</jats:sub> was, therefore, used to define regions of the α<jats:sub>i</jats:sub> subunit polypeptide that conferred selective regulation compared to the α<jats:sub>s</jats:sub> polypeptide. A series of α subunit chimeras having NH<jats:sub>2</jats:sub>‐terminal α<jats:sub>i</jats:sub> and COOH‐terminal α<jats:sub>s</jats:sub> sequences were characterized for their regulation by βγ<jats:sub>t</jats:sub>, measured by the kinetics of GTPγS activation of adenylyl cyclase. A 122 amino acid NH<jats:sub>2</jats:sub>‐terminal region of the α<jats:sub>i</jats:sub> polypeptide encoded within an α<jats:sub>i</jats:sub>/α<jats:sub>s</jats:sub> chimera was sufficient for βγ<jats:sub>t</jats:sub> to discriminate the chimera from α<jats:sub>s</jats:sub>. A shorter 54 amino acid α<jats:sub>i</jats:sub> sequence substituted for the corresponding NH<jats:sub>2</jats:sub>‐terminal region of α<jats:sub>s</jats:sub> was insufficient to support the α<jats:sub>i</jats:sub>‐like interaction with βγ<jats:sub>t</jats:sub>. The findings are consistent with our previous observation (Osawa et al: Cell 63:697–706, 1990) that a region in the NH<jats:sub>2</jats:sub>‐terminal moiety functions as an attenuator domain controlling GDP dissociation and GTP activation of the α subunit polypeptide and that the attenuator domain is involved in functional recognition and regulation by βγ complexes.</jats:p>","journal":"Journal of Cellular Biochemistry","year":1991,"id":25744,"datarank":0.5631408657608294,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.23355717916039642,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.23355717916039642,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":6,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":150678,"name":"Shoji Osawa","orcid":null,"position":1,"is_corresponding":false},{"id":2220,"name":"Gary L. Johnson","orcid":"0000-0003-2867-0551","position":2,"is_corresponding":false},{"id":150677,"name":"N. Dhanasekaran","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"1795017","pmcid":null,"openalex_id":"https://openalex.org/W1971365486","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM 30324","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK 37871","title":null}],"total_grants":2,"fwci":0.4252,"citation_percentile":0.56903234,"influential_citations":0,"citation_trend":[{"year":2016,"count":1}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcb.240470409","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcb.240470409","host_type":"publisher"},{"url":"https://doi.org/10.1002/jcb.240470409","host_type":"journal"}],"fields_of_study":["Protein Kinase Regulation and GTPase Signaling","Retinal Development and Disorders","Cellular transport and secretion","Biology","Chemistry","Adenylyl Cyclases","Animals","Cattle","Cell Line","Chimera","GTP-Binding Proteins","Guanosine 5'-O-(3-Thiotriphosphate)","Rod Cell Outer Segment"],"mesh_terms":["Cell Line","Animals","Chimera","Cattle","GTP-Binding Proteins","Guanosine 5'-O-(3-Thiotriphosphate)","Rod Cell Outer Segment","Adenylyl Cyclases"],"keywords":["G alpha subunit","Adenylyl cyclase","Gi alpha subunit","Gamma subunit","Heterotrimeric G protein","Interleukin 10 receptor, alpha subunit","Transducin","Protein subunit","G protein","Gs alpha subunit","Interleukin 5 receptor alpha subunit","SCN3A","Biology","Alpha (finance)","GTP'","Molecular biology","BETA (programming language)","G beta-gamma complex","GTP-binding protein regulators","Biochemistry","Receptor","Enzyme","Gene","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T07:37:15.620582Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}