Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 4, 2023

Abstract GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

Опубликована: Июль 21, 2023

Abstract GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

Опубликована: Окт. 30, 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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Reviewer #2 (Public Review): Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

Опубликована: Окт. 30, 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The 'self-acting' (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas 'interface-acting' (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding 'poisoning' plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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Reviewer #2 (Public Review): Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

Опубликована: Окт. 30, 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The ‘self-acting’ (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas ‘interface-acting’ (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding ‘poisoning’ plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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Reviewer #1 (Public Review): Interface-acting nucleotide controls polymerization dynamics at microtubule plus- and minus-ends

Опубликована: Окт. 30, 2023

GTP-tubulin is preferentially incorporated at growing microtubule ends, but the biochemical mechanism by which bound nucleotide regulates strength of tubulin:tubulin interactions debated. The 'self-acting' (cis) model posits that (GTP or GDP) to a particular tubulin dictates how strongly interacts, whereas 'interface-acting' (trans) interface two dimers determinant. We identified testable difference between these mechanisms using mixed simulations elongation: with self-acting nucleotide, plus- and minus-end growth rates decreased in same proportion amount GDP-tubulin, interface-acting plus-end disproportionately. then experimentally measured elongation nucleotides observed disproportionate effect GDP-tubulin on rates. Simulations were consistent binding 'poisoning' plus-ends not minus-ends. Quantitative agreement experiments required exchange terminal subunits mitigate poisoning there. Our results indicate interfacial determines interaction strength, thereby settling longstanding debate over state dynamics.

Язык: Английский

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