{"doi":"10.1016/j.jbc.2021.101157","title":"Direct detection of the myosin super-relaxed state and interacting-heads motif in solution","abstract":"The interacting-heads motif (IHM) is a structure of myosin that has been proposed to modulate cardiac output by occluding myosin molecules from undergoing the force-generating cycle. It is hypothesized to be the structural basis for the super-relaxed state (SRX), a low-ATPase kinetic state thought to be cardioprotective. The goal of the present study was to test this hypothesis by determining directly and quantitatively the fractions of myosin in the IHM and SRX under the same conditions in solution. To detect the structural IHM, we used time-resolved fluorescence resonance energy transfer to quantitate two distinct populations. One population was observed at a center distance of 2.0 nm, whereas the other was not detectable by fluorescence resonance energy transfer, implying a distance greater than 4 nm. We confirmed the IHM assignment to the 2.0-nm population by applying the same cross-linking protocol used previously to image the IHM by electron microscopy. Under the same conditions, we also measured the fraction of myosin in the SRX using stopped-flow kinetics. Our results show that the populations of SRX and IHM myosin were similar, a that to and is proposed to by the SRX and we that a greater the SRX than the IHM We that the IHM structure is not to the SRX kinetic The interacting-heads motif (IHM) is a structure of myosin that has been proposed to modulate cardiac output by occluding myosin molecules from undergoing the force-generating cycle. It is hypothesized to be the structural basis for the super-relaxed state (SRX), a low-ATPase kinetic state thought to be cardioprotective. The goal of the present study was to test this hypothesis by determining directly and quantitatively the fractions of myosin in the IHM and SRX under the same conditions in solution. To detect the structural IHM, we used time-resolved fluorescence resonance energy transfer to quantitate two distinct populations. One population was observed at a center distance of 2.0 nm, whereas the other was not detectable by fluorescence resonance energy transfer, implying a distance greater than 4 nm. We confirmed the IHM assignment to the 2.0-nm population by applying the same cross-linking protocol used previously to image the IHM by electron microscopy. Under the same conditions, we also measured the fraction of myosin in the SRX using stopped-flow kinetics. Our results show that the populations of SRX and IHM myosin were similar, a that to and is proposed to by the SRX and we that a greater the SRX than the IHM We that the IHM structure is not to the SRX kinetic is a that the of structural is by and the It of a of two the and and myosin to of the of the The from the to two a and a that and of the of the has to in myosin two It is proposed that the structural basis for this state is the interacting-heads motif (IHM) of a myosin in the motif has been a of myosin the of from a myosin interacting-heads motif and and for myosin in for the IHM has been in of myosin from electron motif has been a of myosin the of and for myosin in structure of cardiac myosin structure in and has been observed by by is by in myosin not the state of myosin cardiac and fluorescence is a in of the of in the IHM, the of the myosin of the the of the motif has been a of myosin the of of in the IHM is the of the is proposed to the of the to the The and the motif of myosin The myosin and the basis of by that in this the of the for the IHM The myosin and the basis of by The present study a of the of the that the the and other that the has been hypothesized that the IHM is the structural basis for the super-relaxed state (SRX), a state by than and to than is for of the myosin molecules in state of cardiac myosin in the is a in in SRX is in the in fluorescence that is from and by in a in the is to the SRX state state of cardiac myosin in the kinetic has also been observed in myosin molecules and state of cardiac It is that the SRX kinetic state to the IHM structural this has not been direct","journal":"Journal of Biological Chemistry","year":2021,"id":155835,"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":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9659,"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":648488,"name":"Joseph M. Muretta","orcid":"0000-0002-3026-4598","position":1,"is_corresponding":false},{"id":417547,"name":"David D. Thomas","orcid":"0000-0002-8822-2040","position":2,"is_corresponding":false},{"id":658952,"name":"Sami Chu","orcid":"0000-0001-7456-2784","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-18T23:44:03.750995Z","pmid":"34481842","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":[]}