{"doi":"10.1101/2021.01.06.425565","title":"The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane","abstract":"Summary Tumor suppressor PTEN, the second most highly mutated protein in cancer, dephosphorylates signaling lipid PIP 3 produced by PI3Ks. Excess PIP 3 promotes cell proliferation. The mechanism at the membrane of this pivotal phosphatase is unknown hindering drug discovery. Exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane. We observed its interaction with membranes composed of zwitterionic phosphatidylcholine, anionic phosphatidylserine, and phosphoinositides, including signaling lipids PIP 2 and PIP 3 . We tracked it’s moving away from the zwitterionic and getting absorbed onto anionic membrane that harbors PIP 3 . We followed it localizing on microdomains enriched in signaling lipids, as PI3K does, and observed PIP 3 allosterically unfolding the N-terminal PIP 2 binding domain, positioning it favorably for the polybasic motif interaction with PIP 2 . Finally, we determined PTEN catalytic action at the membrane, all in line with experimental observations, deciphering the mechanisms of how PTEN anchors to the membrane and restrains cancer.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":218275,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653602,"name":"Iris Nira Smith","orcid":"0000-0001-5560-8871","position":1,"is_corresponding":false},{"id":228051,"name":"Charis Eng","orcid":"0000-0002-3693-5145","position":2,"is_corresponding":false},{"id":70301,"name":"Ruth Nussinov","orcid":"0000-0002-8115-6415","position":3,"is_corresponding":false},{"id":249368,"name":"Hyunbum Jang","orcid":"0000-0001-9402-4051","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:53:29.626149Z","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":[]}