{"doi":"10.1073/pnas.0805852105","title":"Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding","abstract":"<jats:p>\n                    On starvation,\n                    <jats:italic>Dictyostelium</jats:italic>\n                    cells aggregate to form multicellular fruiting bodies containing spores that germinate when transferred to nutrient-rich medium. This developmental cycle correlates with the extent of actin phosphorylation at Tyr-53 (pY53-actin), which is low in vegetative cells but high in viable mature spores. Here we describe high-resolution crystal structures of pY53-actin and unphosphorylated actin in complexes with gelsolin segment 1 and profilin. In the structure of pY53-actin, the phosphate group on Tyr-53 makes hydrogen-bonding interactions with residues of the DNase I-binding loop (D-loop) of actin, resulting in a more stable conformation of the D-loop than in the unphosphorylated structures. A more rigidly folded D-loop may explain some of the previously described properties of pY53-actin, including its increased critical concentration for polymerization, reduced rates of nucleation and pointed end elongation, and weak affinity for DNase I. We show here that phosphorylation of Tyr-53 inhibits subtilisin cleavage of the D-loop and reduces the rate of nucleotide exchange on actin. The structure of profilin–\n                    <jats:italic>Dictyostelium</jats:italic>\n                    -actin is strikingly similar to previously determined structures of profilin–β-actin and profilin–α-actin. By comparing this representative set of profilin–actin structures with other structures of actin, we highlight the effects of profilin on the actin conformation. In the profilin–actin complexes, subdomains 1 and 3 of actin close around profilin, producing a 4.7° rotation of the two major domains of actin relative to each other. As a result, the nucleotide cleft becomes moderately more open in the profilin–actin complex, probably explaining the stimulation of nucleotide exchange on actin by profilin.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2008,"id":637202,"datarank":0.6284482113039639,"base_score":4.189654742026425,"endowment":4.189654742026425,"self_citation_contribution":0.6284482113039639,"citation_network_contribution":0.0,"self_endowment_contribution":0.6284482113039639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1404124,"name":"Xiong Liu","orcid":"0000-0002-3631-9940","position":1,"is_corresponding":false},{"id":1654335,"name":"François Ferron","orcid":null,"position":2,"is_corresponding":false},{"id":1034525,"name":"Shi Shu","orcid":"0000-0002-9982-4215","position":3,"is_corresponding":false},{"id":1654338,"name":"Edward D. Korn","orcid":null,"position":4,"is_corresponding":false},{"id":1654339,"name":"Roberto Dominguez","orcid":null,"position":5,"is_corresponding":false},{"id":924381,"name":"Kyuwon Baek","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Modulation of actin structure and function by phosphorylation of Tyr-53 and profilin binding","abstract":"<jats:p>\n                    On starvation,\n                    <jats:italic>Dictyostelium</jats:italic>\n                    cells aggregate to form multicellular fruiting bodies containing spores that germinate when transferred to nutrient-rich medium. This developmental cycle correlates with the extent of actin phosphorylation at Tyr-53 (pY53-actin), which is low in vegetative cells but high in viable mature spores. Here we describe high-resolution crystal structures of pY53-actin and unphosphorylated actin in complexes with gelsolin segment 1 and profilin. In the structure of pY53-actin, the phosphate group on Tyr-53 makes hydrogen-bonding interactions with residues of the DNase I-binding loop (D-loop) of actin, resulting in a more stable conformation of the D-loop than in the unphosphorylated structures. A more rigidly folded D-loop may explain some of the previously described properties of pY53-actin, including its increased critical concentration for polymerization, reduced rates of nucleation and pointed end elongation, and weak affinity for DNase I. We show here that phosphorylation of Tyr-53 inhibits subtilisin cleavage of the D-loop and reduces the rate of nucleotide exchange on actin. The structure of profilin–\n                    <jats:italic>Dictyostelium</jats:italic>\n                    -actin is strikingly similar to previously determined structures of profilin–β-actin and profilin–α-actin. By comparing this representative set of profilin–actin structures with other structures of actin, we highlight the effects of profilin on the actin conformation. In the profilin–actin complexes, subdomains 1 and 3 of actin close around profilin, producing a 4.7° rotation of the two major domains of actin relative to each other. As a result, the nucleotide cleft becomes moderately more open in the profilin–actin complex, probably explaining the stimulation of nucleotide exchange on actin by profilin.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.189654742026425,"endowment":4.189654742026425,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18689676","pmcid":null,"openalex_id":"https://openalex.org/W2167793055","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM073791","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"DMR-0225180","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"RR-01646","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM073791","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"P41 RR001646","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"","title":null}],"total_grants":6,"fwci":1.6481,"citation_percentile":0.82194849,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":4},{"year":2014,"count":4},{"year":2015,"count":1},{"year":2016,"count":2},{"year":2017,"count":5},{"year":2018,"count":3},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":5},{"year":2022,"count":2},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2575267","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2575267","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0805852105","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0805852105","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18689676","host_type":"repository"}],"fields_of_study":["Cellular Mechanics and Interactions","Spaceflight effects on biology","Biocrusts and Microbial Ecology","Actins","Animals","Crystallography, X-Ray","Dictyostelium","Humans","Models, Molecular","Phosphorylation","Profilins","Protein Binding","Protein Structure, Quaternary","Protein Structure, Tertiary","Tyrosine"],"mesh_terms":["Actins","Animals","Dictyostelium","Humans","Models, Molecular","Phosphorylation","Protein Binding","Tyrosine","Protein Structure, Tertiary","Crystallography, X-Ray","Protein Structure, Quaternary","Profilins"],"keywords":["Profilin","Actin remodeling","MDia1","Actin-binding protein","Actin","Actin remodeling of neurons","Gelsolin","Biology","Cell biology","Microfilament","Biophysics","Biochemistry","Chemistry","Actin cytoskeleton","Cytoskeleton","Cell"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T18:31:02.382447Z","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":[]}