{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["118(1)"],"submitter":["Warias M"],"pubmed_abstract":["In each round of ribosomal translation, the translational GTPase elongation factor Tu (EF-Tu) delivers a transfer RNA (tRNA) to the ribosome. After successful decoding, EF-Tu hydrolyzes GTP, which triggers a conformational change that ultimately results in the release of the tRNA from EF-Tu. To identify the primary steps of these conformational changes and how they are prevented by the antibiotic kirromycin, we employed all-atom explicit-solvent molecular dynamics simulations of the full ribosome-EF-Tu complex. Our results suggest that after GTP hydrolysis and P<sub>i</sub> release, the loss of interactions between the nucleotide and the switch 1 loop of EF-Tu allows domain D1 of EF-Tu to rotate relative to domains D2 and D3 and leads to an increased flexibility of the switch 1 loop. This rotation induces a closing of the D1-D3 interface and an opening of the D1-D2 interface. We propose that the opening of the D1-D2 interface, which binds the CCA tail of the tRNA, weakens the crucial EF-Tu-tRNA interactions, which lowers tRNA binding affinity, representing the first step of tRNA release. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. The resulting increased flexibility of switch 1 explains why it is not resolved in kirromycin-bound structures."],"journal":["Biophysical journal"],"pagination":["151-161"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6950810"],"repository":["biostudies-literature"],"pubmed_title":["tRNA Dissociation from EF-Tu after GTP Hydrolysis: Primary Steps and Antibiotic Inhibition."],"pmcid":["PMC6950810"],"pubmed_authors":["Warias M","Grubmuller H","Bock LV"],"additional_accession":[]},"is_claimable":false,"name":"tRNA Dissociation from EF-Tu after GTP Hydrolysis: Primary Steps and Antibiotic Inhibition.","description":"In each round of ribosomal translation, the translational GTPase elongation factor Tu (EF-Tu) delivers a transfer RNA (tRNA) to the ribosome. After successful decoding, EF-Tu hydrolyzes GTP, which triggers a conformational change that ultimately results in the release of the tRNA from EF-Tu. To identify the primary steps of these conformational changes and how they are prevented by the antibiotic kirromycin, we employed all-atom explicit-solvent molecular dynamics simulations of the full ribosome-EF-Tu complex. Our results suggest that after GTP hydrolysis and P<sub>i</sub> release, the loss of interactions between the nucleotide and the switch 1 loop of EF-Tu allows domain D1 of EF-Tu to rotate relative to domains D2 and D3 and leads to an increased flexibility of the switch 1 loop. This rotation induces a closing of the D1-D3 interface and an opening of the D1-D2 interface. We propose that the opening of the D1-D2 interface, which binds the CCA tail of the tRNA, weakens the crucial EF-Tu-tRNA interactions, which lowers tRNA binding affinity, representing the first step of tRNA release. Kirromycin binds within the D1-D3 interface, sterically blocking its closure, but does not prevent hydrolysis. The resulting increased flexibility of switch 1 explains why it is not resolved in kirromycin-bound structures.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2024-11-20T08:26:46.544Z","creation":"2020-10-29T09:16:13Z"},"accession":"S-EPMC6950810","cross_references":{"pubmed":["31711607"],"doi":["10.1016/j.bpj.2019.10.028"]}}