{"doi":"10.1101/2022.06.10.495627","title":"<i>Cis</i>\n                  -membrane association of human ATG8 proteins N-terminus mediates autophagy","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Autophagy is an essential catabolic pathway which sequesters and engulfs cytosolic substrates via autophagosomes, unique double-membraned structures. ATG8 proteins are ubiquitin-like proteins recruited to autophagosome membranes by lipidation at the C-terminus. ATG8s recruit substrates, such as p62, and play an important role in mediating autophagosome membrane expansion. However, the precise function of lipidated ATG8 in expansion remains obscure. Using a real-time\n                  <jats:italic>in vitro</jats:italic>\n                  lipidation assay, we revealed that the N-termini of lipidated human ATG8s (LC3B and GABARAP) are highly dynamic and interact with the membrane. Moreover, atomistic MD simulation and FRET assays indicate that N-termini of LC3B and GABARAP associate\n                  <jats:italic>in cis</jats:italic>\n                  on the membrane. The\n                  <jats:italic>cis</jats:italic>\n                  -membrane association of the N-terminus is critical to maintain membrane expansion and the size of autophagosomes in cells, consequently, mediating the efficient degradation of p62. Our study provides fundamental molecular insights into autophagosome membrane expansion, revealing the critical and unique function of lipidated ATG8.\n                </jats:p>","journal":null,"year":null,"id":604706,"datarank":0.2872507072162216,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.018486786832013314,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.018486786832013314,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"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":127495,"name":"Taki Nishimura","orcid":null,"position":1,"is_corresponding":false},{"id":1213354,"name":"Deepanshi Gahlot","orcid":"0000-0002-2681-8818","position":2,"is_corresponding":false},{"id":1551601,"name":"Chieko Saito","orcid":null,"position":3,"is_corresponding":false},{"id":1551602,"name":"Colin Davis","orcid":null,"position":4,"is_corresponding":false},{"id":1551603,"name":"Harold B. J. Jefferies","orcid":null,"position":5,"is_corresponding":false},{"id":1551604,"name":"Anne Schreiber","orcid":null,"position":6,"is_corresponding":false},{"id":851121,"name":"Lipi Thukral","orcid":"0000-0002-1961-039X","position":7,"is_corresponding":false},{"id":639023,"name":"Sharon A. Tooze","orcid":"0000-0002-2182-3116","position":8,"is_corresponding":false},{"id":1459516,"name":"Wenxin Zhang","orcid":"0000-0001-9937-6240","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>Cis</i>\n                  -membrane association of human ATG8 proteins N-terminus mediates autophagy","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Autophagy is an essential catabolic pathway which sequesters and engulfs cytosolic substrates via autophagosomes, unique double-membraned structures. ATG8 proteins are ubiquitin-like proteins recruited to autophagosome membranes by lipidation at the C-terminus. ATG8s recruit substrates, such as p62, and play an important role in mediating autophagosome membrane expansion. However, the precise function of lipidated ATG8 in expansion remains obscure. Using a real-time\n                  <jats:italic>in vitro</jats:italic>\n                  lipidation assay, we revealed that the N-termini of lipidated human ATG8s (LC3B and GABARAP) are highly dynamic and interact with the membrane. Moreover, atomistic MD simulation and FRET assays indicate that N-termini of LC3B and GABARAP associate\n                  <jats:italic>in cis</jats:italic>\n                  on the membrane. The\n                  <jats:italic>cis</jats:italic>\n                  -membrane association of the N-terminus is critical to maintain membrane expansion and the size of autophagosomes in cells, consequently, mediating the efficient degradation of p62. Our study provides fundamental molecular insights into autophagosome membrane expansion, revealing the critical and unique function of lipidated ATG8.\n                </jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W4281769815","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":3},{"year":2024,"count":2}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/06/10/2022.06.10.495627.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/06/10/2022.06.10.495627.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.06.10.495627","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.06.10.495627","host_type":"repository"}],"fields_of_study":["Autophagy in Disease and Therapy","RNA Interference and Gene Delivery","Cellular transport and secretion"],"mesh_terms":[],"keywords":["ATG8","Lipid-anchored protein","Autophagosome","Autophagy","Cell biology","Membrane","Ubiquitin","Chemistry","Biology","Biochemistry","Apoptosis"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T00:45:35.023490Z","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":[]}