{"doi":"10.1101/2023.06.20.545612","title":"RAS G-domains fine-tune the sorting of phosphatidylserine acyl chains in the plasma membrane","abstract":"Abstract Mutant RAS are major contributors to cancer and signal from nanoclusters on the plasma membrane (PM), via isoform-specific membrane anchors. However, the same RAS isoform bound to different guanine nucleotides are segregated on the PM. Paradoxically, various segregated RAS nanoclusters all enrich a type of anionic phospholipid, phosphatidylserine (PS). These findings suggest intricate participation of RAS G-domains in their PM distribution, which have not been explored. We now show that wild-types, oncogenic G12V mutants and membrane anchors of isoforms HRAS, KRAS4A and KRAS4B sort distinct PS species. Mechanistically, shifting orientation states of KRAS4B G-domain exposes residues, such as Arg 73, Arg 102 and Arg 135, to the PM, and contributes to PS acyl chain sorting. Oncogenic mutations may shift orientation states of G-domains. We show that G12V, G12D, G12C, G13D and Q61H mutants of KRAS4B sort distinct PS species. Thus, RAS G-domains fine-tune their lateral distribution on the PM.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399913,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302569,"name":"Liang Hong","orcid":"0000-0003-1101-7046","position":1,"is_corresponding":false},{"id":302566,"name":"Yong Zhou","orcid":"0000-0002-0214-8151","position":2,"is_corresponding":false},{"id":992384,"name":"Neha Arora","orcid":"0000-0001-9198-8744","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","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":[]}