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Kinesin-2 heterodimerization alters entry into a processive run along the microtubule but not stepping within the run.


ABSTRACT: Heterodimeric KIF3AC and KIF3AB, two members of the mammalian kinesin-2 family, generate force for microtubule plus end-directed cargo transport. However, the advantage of heterodimeric kinesins over homodimeric ones is not well-understood. We showed previously that microtubule association for entry into a processive run was similar in rate for KIF3AC and KIF3AB at ?7.0 ?m-1 s-1 Yet, for engineered homodimers of KIF3AA and KIF3BB, this constant is significantly faster at 11 ?m-1 s-1 and much slower for KIF3CC at 2.1 ?m-1 s-1 These results led us to hypothesize that heterodimerization of KIF3A with KIF3C and KIF3A with KIF3B altered the intrinsic catalytic properties of each motor domain. Here, we tested this hypothesis by using presteady-state stopped-flow kinetics and mathematical modeling. Surprisingly, the modeling revealed that the catalytic properties of KIF3A and KIF3B/C were altered upon microtubule binding, yet each motor domain retained its relative intrinsic kinetics for ADP release and subsequent ATP binding and the nucleotide-promoted transitions thereafter. These results are consistent with the interpretation that for KIF3AB, each motor head is catalytically similar and therefore each step is approximately equivalent. In contrast, for KIF3AC the results predict that the processive steps will alternate between a fast step for KIF3A followed by a slow step for KIF3C resulting in asymmetric stepping during a processive run. This study reveals the impact of heterodimerization of the motor polypeptides for microtubule association to start the processive run and the fundamental differences in the motile properties of KIF3C compared with KIF3A and KIF3B.

SUBMITTER: Quinn SM 

PROVIDER: S-EPMC6120217 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Kinesin-2 heterodimerization alters entry into a processive run along the microtubule but not stepping within the run.

Quinn Sean M SM   Howsmon Daniel P DP   Hahn Juergen J   Gilbert Susan P SP  

The Journal of biological chemistry 20180710 35


Heterodimeric KIF3AC and KIF3AB, two members of the mammalian kinesin-2 family, generate force for microtubule plus end-directed cargo transport. However, the advantage of heterodimeric kinesins over homodimeric ones is not well-understood. We showed previously that microtubule association for entry into a processive run was similar in rate for KIF3AC and KIF3AB at ∼7.0 μm<sup>-1</sup> s<sup>-1</sup> Yet, for engineered homodimers of KIF3AA and KIF3BB, this constant is significantly faster at 11  ...[more]

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