{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["McCormick LA"],"funding":["National Institute of General Medical Sciences","NIGMS NIH HHS","National Science Foundation"],"pagination":["RP89231"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945504"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which the bound nucleotide regulates the strength of tubulin:tubulin interactions is debated. The 'self-acting' (cis) model posits that the nucleotide (GTP or GDP) bound to a particular tubulin dictates how strongly that tubulin interacts, whereas the 'interface-acting' (trans) model posits that the nucleotide at the interface of two tubulin dimers is the determinant. We identified a testable difference between these mechanisms using mixed nucleotide simulations of microtubule elongation: with a self-acting nucleotide, plus- and minus-end growth rates decreased in the same proportion to the amount of GDP-tubulin, whereas with interface-acting nucleotide, plus-end growth rates decreased disproportionately. We then experimentally measured plus- and minus-end elongation rates in mixed nucleotides and observed a disproportionate effect of GDP-tubulin on plus-end growth rates. Simulations of microtubule growth were consistent with GDP-tubulin binding at and 'poisoning' plus-ends but not at minus-ends. Quantitative agreement between simulations and experiments required nucleotide exchange at terminal plus-end subunits to mitigate the poisoning effect of GDP-tubulin there. Our results indicate that the interfacial nucleotide determines tubulin:tubulin interaction strength, thereby settling a longstanding debate over the effect of nucleotide state on microtubule dynamics."],"journal":["eLife"],"pubmed_title":["Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends."],"pmcid":["PMC10945504"],"funding_grant_id":["T32-GM108563","R35 GM139568","T32 GM108563","R35-GM139568","R01-GM135565","R01 GM135565","PRFB 2209298"],"pubmed_authors":["Hancock WO","McCormick LA","Rice LM","Cleary JM"],"additional_accession":[]},"is_claimable":false,"name":"Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends.","description":"GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which the bound nucleotide regulates the strength of tubulin:tubulin interactions is debated. The 'self-acting' (cis) model posits that the nucleotide (GTP or GDP) bound to a particular tubulin dictates how strongly that tubulin interacts, whereas the 'interface-acting' (trans) model posits that the nucleotide at the interface of two tubulin dimers is the determinant. We identified a testable difference between these mechanisms using mixed nucleotide simulations of microtubule elongation: with a self-acting nucleotide, plus- and minus-end growth rates decreased in the same proportion to the amount of GDP-tubulin, whereas with interface-acting nucleotide, plus-end growth rates decreased disproportionately. We then experimentally measured plus- and minus-end elongation rates in mixed nucleotides and observed a disproportionate effect of GDP-tubulin on plus-end growth rates. Simulations of microtubule growth were consistent with GDP-tubulin binding at and 'poisoning' plus-ends but not at minus-ends. Quantitative agreement between simulations and experiments required nucleotide exchange at terminal plus-end subunits to mitigate the poisoning effect of GDP-tubulin there. Our results indicate that the interfacial nucleotide determines tubulin:tubulin interaction strength, thereby settling a longstanding debate over the effect of nucleotide state on microtubule dynamics.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2025-05-18T12:54:27.798Z","creation":"2025-05-18T12:54:27.798Z"},"accession":"S-EPMC10945504","cross_references":{"pubmed":["38180336"],"doi":["10.7554/eLife.89231"]}}