Publication Date:
2019
Description:
〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉
〈p〉The movement of dynein on microtubules requires communication between enzymatic, polymer-binding, and mechanical elements. Our results reveal how dynein's coiled-coil stalk plays a critical role in coordinating such domain movements.〈/p〉
〈p〉 〈l type="unord"〉〈li〉〈p〉Stalk mutants disrupt unidirectional motion along microtubules, show nucleotide-independent low affinity for microtubules, and lack microtubule-regulation of ATPase activity.〈/p〉〈/li〉
〈li〉〈p〉Cryo-electron microscopy structures of one mutant show that nucleotide-dependent conformational changes are disrupted in one half of the AAA ring while the other half is minimally affected; the partial ring conformational change results in unregulated ATP hydrolysis and blocks the linker conformational change that drives motility.〈/p〉〈/li〉
〈li〉〈p〉Our structural and functional results suggest a model for how the stalk domain modulates conformational changes around the AAA ring, which are initiated by nucleotide binding at dynein's main ATP site (AAA1).〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
Print ISSN:
0261-4189
Electronic ISSN:
1460-2075
Topics:
Biology
,
Medicine
