{"doi":"10.1101/2021.08.03.454958","title":"Principles of sensor-effector organization in six-transmembrane ion channels","abstract":"Abstract Receptor proteins sense stimuli and generate downstream signals via sensor and effector domains. Presently, the structural constraints on sensor-effector organization across receptor protein superfamilies are not clear. Here, we perform statistical coupling analysis (SCA) on the transient receptor potential (TRP) and voltage-gated potassium (Kv) ion channel superfamilies to characterize the networks of coevolving residues, or protein sectors, that mediate their receptor functions. Comparisons to structural and functional studies reveal a conserved “core” sector that extends from the pore and mediates effector functions, including pore gating and sensor-pore coupling, while sensors correspond to family-specific “accessory” sectors and localize according to three principles: Sensors (1) may emerge in any region with access to the core, (2) must maintain contact with the core, and (3) must preserve the integrity of the core. This sensor-core architecture may represent a conserved and generalizable paradigm for the structure-function relationships underlying the evolution of receptor proteins.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225949,"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":0.9531,"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":321387,"name":"Po Wei Kang","orcid":"0000-0002-5933-545X","position":1,"is_corresponding":false},{"id":321388,"name":"Panpan Hou","orcid":"0000-0001-7694-2262","position":2,"is_corresponding":false},{"id":797451,"name":"Mark A. Zaydman","orcid":"0000-0002-4236-1459","position":3,"is_corresponding":false},{"id":284446,"name":"Jie Zheng","orcid":"0000-0002-4161-627X","position":4,"is_corresponding":false},{"id":427859,"name":"Timothy Jegla","orcid":"0000-0001-8616-2390","position":5,"is_corresponding":false},{"id":321395,"name":"Jianmin Cui","orcid":"0000-0002-9198-6332","position":6,"is_corresponding":false},{"id":561637,"name":"Alex Dou","orcid":"0000-0001-7446-1676","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T23:54:30.292454Z","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":[]}