{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zinder JC"],"funding":["HHS | National Institutes of Health","Howard Hughes Medical Institute","HHS | NIH | National Cancer Institute","NCI NIH HHS","Damon Runyon Cancer Research Foundation","NIGMS NIH HHS"],"pagination":["e2201662119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9351484"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(31)"],"pubmed_abstract":["Human shelterin is a six-subunit complex-composed of TRF1, TRF2, Rap1, TIN2, TPP1, and POT1-that binds telomeres, protects them from the DNA-damage response, and regulates the maintenance of telomeric DNA. Although high-resolution structures have been generated of the individual structured domains within shelterin, the architecture and stoichiometry of the full complex are currently unknown. Here, we report the purification of shelterin subcomplexes and reconstitution of the entire complex using full-length, recombinant subunits. By combining negative-stain electron microscopy (EM), cross-linking mass spectrometry (XLMS), AlphaFold modeling, mass photometry, and native mass spectrometry (MS), we obtain stoichiometries as well as domain-scale architectures of shelterin subcomplexes and dete"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Shelterin is a dimeric complex with extensive structural heterogeneity."],"pmcid":["PMC9351484"],"funding_grant_id":["5 R35 CA210036","R35 CA210036","DRG 2337-19","P41 GM103314","P41 GM109824","T32 CA009673"],"pubmed_authors":["Chait BT","Walz T","Bush MW","Olinares PDB","Zinder JC","Nudler E","Svetlov V","de Lange T"],"additional_accession":[]},"is_claimable":false,"name":"Shelterin is a dimeric complex with extensive structural heterogeneity.","description":"Human shelterin is a six-subunit complex-composed of TRF1, TRF2, Rap1, TIN2, TPP1, and POT1-that binds telomeres, protects them from the DNA-damage response, and regulates the maintenance of telomeric DNA. Although high-resolution structures have been generated of the individual structured domains within shelterin, the architecture and stoichiometry of the full complex are currently unknown. Here, we report the purification of shelterin subcomplexes and reconstitution of the entire complex using full-length, recombinant subunits. By combining negative-stain electron microscopy (EM), cross-linking mass spectrometry (XLMS), AlphaFold modeling, mass photometry, and native mass spectrometry (MS), we obtain stoichiometries as well as domain-scale architectures of shelterin subcomplexes and dete","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Aug","modification":"2025-04-27T01:10:56.25Z","creation":"2025-02-19T04:53:44.506Z"},"accession":"S-EPMC9351484","cross_references":{"pubmed":["35881804"],"doi":["10.1073/pnas.2201662119"]}}