{"doi":"10.1074/jbc.ra119.011389","title":"“Register-shift” insulin analogs uncover constraints of proteotoxicity in protein evolution","abstract":"]insulin) was as potent as WT insulin in a rat model of diabetes. Although in MD simulations the shifted register of receptor engagement is compatible with the structure and allosteric reorganization of the IR-signaling complex, our results suggest that this binding mode is associated with toxic misfolding and so is disallowed in evolution. The implicit threat of proteotoxicity limits sequence variation among vertebrate insulins and insulin-like growth factors.","journal":"Journal of Biological Chemistry","year":2020,"id":80015,"datarank":0.493735001910046,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.07784669357407875,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.07784669357407875,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"is_data_producer":true,"deposit_databanks":{"PDB":["4OGA","4INS","2KJJ"]},"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":289733,"name":"Ming Liu","orcid":"0000-0003-2665-4072","position":1,"is_corresponding":false},{"id":338985,"name":"Balamurugan Dhayalan","orcid":"0000-0001-6002-1207","position":2,"is_corresponding":false},{"id":338987,"name":"Yen‐Shan Chen","orcid":"0000-0003-4746-6636","position":3,"is_corresponding":false},{"id":415450,"name":"Nicholas A. Smith","orcid":"0000-0001-8894-4249","position":4,"is_corresponding":false},{"id":338988,"name":"Leili Rahimi","orcid":"0000-0002-3908-8324","position":5,"is_corresponding":false},{"id":184322,"name":"Jinhong Sun","orcid":null,"position":6,"is_corresponding":false},{"id":79048,"name":"Huan Guo","orcid":"0000-0002-7838-2585","position":7,"is_corresponding":false},{"id":338984,"name":"Yanwu Yang","orcid":"0000-0002-4832-2987","position":8,"is_corresponding":false},{"id":33712,"name":"Leena Haataja","orcid":"0000-0003-3701-4679","position":9,"is_corresponding":false},{"id":416800,"name":"Nelson F. B. Phillips","orcid":null,"position":10,"is_corresponding":false},{"id":416801,"name":"Jonathan Whittaker","orcid":null,"position":11,"is_corresponding":false},{"id":415451,"name":"Brian J. Smith","orcid":"0000-0003-0498-1910","position":12,"is_corresponding":false},{"id":33730,"name":"Peter Arvan","orcid":"0000-0002-4007-8799","position":13,"is_corresponding":false},{"id":63114,"name":"Faramarz Ismail‐Beigi","orcid":"0000-0002-1154-5482","position":14,"is_corresponding":false},{"id":338990,"name":"Michael A. Weiss","orcid":"0000-0003-1325-1610","position":15,"is_corresponding":false},{"id":338983,"name":"Nischay Rege","orcid":"0000-0002-3858-9530","position":0,"is_corresponding":true}],"reference_count":132,"raw_metadata":null,"created_at":"2026-07-18T21:51:24.704381Z","pmid":"32005662","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":[]}