{"doi":"10.17615/dy5d-v834","title":"Structure of Gαi1 Bound to a GDP-Selective Peptide Provides Insight into Guanine Nucleotide Exchange","abstract":"Heterotrimeric G-proteins are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive, GDP-bound and an active, GTP-bound state. Under basal conditions G-proteins exist in the inactive GDP-bound state, thus nucleotide exchange is crucial to the onset of signaling. Despite our understanding of G-protein signaling pathways, the mechanism of nucleotide exchange remains elusive. We employed phage display technology to identify nucleotide-state-dependent Gα binding peptides. Herein, we report a GDP-selective Gα-binding peptide, KB-752, that enhances spontaneous nucleotide exchange of Gαi subunits. Structural determination of the Gαi1/peptide complex reveals unique changes in the Gα switch regions predicted to enhance nucleotide exchange by creating a GDP dissociation route. Our results cast light onto a potential mechanism by which Gα subunits adopt a conformation suitable for nucleotide exchange.","journal":"UNC Libraries","year":2020,"id":137826,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":599112,"name":"Mark R. Jezyk","orcid":null,"position":1,"is_corresponding":false},{"id":437994,"name":"David P. Siderovski","orcid":"0000-0002-0688-8210","position":2,"is_corresponding":false},{"id":515775,"name":"T. Kendall Harden","orcid":null,"position":3,"is_corresponding":false},{"id":226892,"name":"Francis S. Willard","orcid":"0000-0002-4260-2451","position":4,"is_corresponding":false},{"id":452824,"name":"Val J. Watts","orcid":"0000-0003-1581-2936","position":5,"is_corresponding":false},{"id":599113,"name":"Miller B. Jones","orcid":null,"position":6,"is_corresponding":false},{"id":579220,"name":"J. Kevin Ramer","orcid":null,"position":7,"is_corresponding":false},{"id":599114,"name":"Erik T. Bodor","orcid":null,"position":8,"is_corresponding":false},{"id":30214,"name":"John Sondek","orcid":"0000-0002-1127-8310","position":9,"is_corresponding":false},{"id":579221,"name":"Zoey L. Fredericks","orcid":null,"position":10,"is_corresponding":false},{"id":578792,"name":"Rainer Blaesius","orcid":"0000-0002-5048-9276","position":11,"is_corresponding":false},{"id":436352,"name":"Christopher A. Johnston","orcid":"0000-0001-6255-4648","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","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":[]}