{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Baker MR"],"funding":["NCRR NIH HHS","NIAMS NIH HHS","NIH HHS","NIGMS NIH HHS"],"pagination":["35-48"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4381806"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(1)"],"pubmed_abstract":["Ryanodine receptors (RyRs) are tetrameric ligand-gated Ca2+ release channels that are responsible for the increase of cytosolic Ca2+ concentration leading to muscle contraction. Our current understanding of RyR channel gating and regulation is greatly limited due to the lack of a high-resolution structure of the channel protein. The enormous size and unwieldy shape of Ca2+ release channels make X-ray or NMR methods difficult to apply for high-resolution structural analysis of the full-length functional channel. Single-particle electron cryo-microscopy (cryo-EM) is one of the only effective techniques for the study of such a large integral membrane protein and its molecular interactions. Despite recent developments in cryo-EM technologies and break-through single-particle cryo-EM studies of ion channels, cryospecimen preparation, particularly the presence of detergent in the buffer, remains the main impediment to obtaining atomic-resolution structures of ion channels and a multitude of other integral membrane protein complexes. In this review we will discuss properties of several detergents that have been successfully utilized in cryo-EM studies of ion channels and the emergence of the detergent alternative amphipol to stabilize ion channels for structure-function characterization. Future structural studies of challenging specimen like ion channels are likely to be facilitated by cryo-EM amenable detergents or alternative surfactants."],"journal":["European journal of translational myology"],"pubmed_title":["Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment."],"pmcid":["PMC4381806"],"funding_grant_id":["R21 AR063255","P41 RR002250","S10 OD016279","R01 GM072804"],"pubmed_authors":["Fan G","Baker MR","Serysheva II"],"additional_accession":[]},"is_claimable":false,"name":"Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment.","description":"Ryanodine receptors (RyRs) are tetrameric ligand-gated Ca2+ release channels that are responsible for the increase of cytosolic Ca2+ concentration leading to muscle contraction. Our current understanding of RyR channel gating and regulation is greatly limited due to the lack of a high-resolution structure of the channel protein. The enormous size and unwieldy shape of Ca2+ release channels make X-ray or NMR methods difficult to apply for high-resolution structural analysis of the full-length functional channel. Single-particle electron cryo-microscopy (cryo-EM) is one of the only effective techniques for the study of such a large integral membrane protein and its molecular interactions. Despite recent developments in cryo-EM technologies and break-through single-particle cryo-EM studies of ion channels, cryospecimen preparation, particularly the presence of detergent in the buffer, remains the main impediment to obtaining atomic-resolution structures of ion channels and a multitude of other integral membrane protein complexes. In this review we will discuss properties of several detergents that have been successfully utilized in cryo-EM studies of ion channels and the emergence of the detergent alternative amphipol to stabilize ion channels for structure-function characterization. Future structural studies of challenging specimen like ion channels are likely to be facilitated by cryo-EM amenable detergents or alternative surfactants.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015","modification":"2024-12-04T04:26:47.342Z","creation":"2019-03-26T22:49:07Z"},"accession":"S-EPMC4381806","cross_references":{"pubmed":["25844145"],"doi":["10.4081/ejtm.2015.4803","10.4081/bam.2015.1.35"]}}