{"doi":"10.1101/2020.02.05.936161","title":"Nonspecific membrane interactions can modulate BK channel activation","abstract":"Large-conductance potassium (BK) channels are transmembrane (TM) proteins that can be synergistically and independently activated by membrane voltage and intracellular Ca 2+ . The only covalent connection between the cytosolic Ca 2+ sensing domain and the TM pore and voltage sensing domains is a 15-residue \"C-linker\". To determine the linker's role in BK activation, we designed a series of linker sequence scrambling mutants to suppress potential complex interplay of specific interactions with the rest of the protein. The results revealed a surprising sensitivity of BK activation to the linker sequence. Combing atomistic simulations and further mutagenesis experiments, we demonstrated that nonspecific interactions of the linker with membrane alone could directly modulate BK activation. The C-linker thus plays more direct roles in mediating allosteric coupling between BK domains than previously assumed. Our results also suggest that covalent linkers could directly modulate TM protein function and should be considered an integral component of the sensing apparatus.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128902,"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":0.9543,"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":506034,"name":"Guohui Zhang","orcid":"0000-0001-6905-0637","position":1,"is_corresponding":false},{"id":573965,"name":"Zhiguang Jia","orcid":"0000-0002-9902-4832","position":2,"is_corresponding":false},{"id":321392,"name":"Jingyi Shi","orcid":"0009-0009-5119-8540","position":3,"is_corresponding":false},{"id":321395,"name":"Jianmin Cui","orcid":"0000-0002-9198-6332","position":4,"is_corresponding":false},{"id":238225,"name":"Jianhan Chen","orcid":"0000-0002-5281-1150","position":5,"is_corresponding":false},{"id":579646,"name":"Mahdieh Yazdani","orcid":"0000-0003-1300-4599","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","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":[]}