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Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6.

Publication ,  Journal Article
Ranaivoson, FM; Crozet, V; Benoit, MPMH; Abdalla Mohammed Khalid, A; Kikuti, C; Sirkia, H; El Marjou, A; Miserey-Lenkei, S; Asenjo, AB; Sosa, H ...
Published in: Open biology
September 2023

KIF20A is a critical kinesin for cell division and a promising anti-cancer drug target. The mechanisms underlying its cellular roles remain elusive. Interestingly, unusual coupling between the nucleotide- and microtubule-binding sites of this kinesin-6 has been reported, but little is known about how its divergent sequence leads to atypical motility properties. We present here the first high-resolution structure of its motor domain that delineates the highly unusual structural features of this motor, including a long L6 insertion that integrates into the core of the motor domain and that drastically affects allostery and ATPase activity. Together with the high-resolution cryo-electron microscopy microtubule-bound KIF20A structure that reveals the microtubule-binding interface, we dissect the peculiarities of the KIF20A sequence that influence its mechanochemistry, leading to low motility compared to other kinesins. Structural and functional insights from the KIF20A pre-power stroke conformation highlight the role of extended insertions in shaping the motor's mechanochemical cycle. Essential for force production and processivity is the length of the neck linker in kinesins. We highlight here the role of the sequence preceding the neck linker in controlling its backward docking and show that a neck linker four times longer than that in kinesin-1 is required for the activity of this motor.

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Published In

Open biology

DOI

EISSN

2046-2441

ISSN

2046-2441

Publication Date

September 2023

Volume

13

Issue

9

Start / End Page

230122

Related Subject Headings

  • Microtubules
  • Kinesins
  • Cryoelectron Microscopy
  • Cell Division
  • Binding Sites
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 1107 Immunology
  • 0605 Microbiology
  • 0601 Biochemistry and Cell Biology
 

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Ranaivoson, F. M., Crozet, V., Benoit, M. P. M. H., Abdalla Mohammed Khalid, A., Kikuti, C., Sirkia, H., … Houdusse, A. (2023). Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6. Open Biology, 13(9), 230122. https://doi.org/10.1098/rsob.230122
Ranaivoson, Fanomezana Moutse, Vincent Crozet, Matthieu P. M. H. Benoit, Amna Abdalla Mohammed Khalid, Carlos Kikuti, Helena Sirkia, Ahmed El Marjou, et al. “Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6.Open Biology 13, no. 9 (September 2023): 230122. https://doi.org/10.1098/rsob.230122.
Ranaivoson FM, Crozet V, Benoit MPMH, Abdalla Mohammed Khalid A, Kikuti C, Sirkia H, et al. Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6. Open biology. 2023 Sep;13(9):230122.
Ranaivoson, Fanomezana Moutse, et al. “Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6.Open Biology, vol. 13, no. 9, Sept. 2023, p. 230122. Epmc, doi:10.1098/rsob.230122.
Ranaivoson FM, Crozet V, Benoit MPMH, Abdalla Mohammed Khalid A, Kikuti C, Sirkia H, El Marjou A, Miserey-Lenkei S, Asenjo AB, Sosa H, Schmidt CF, Rosenfeld SS, Houdusse A. Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6. Open biology. 2023 Sep;13(9):230122.
Journal cover image

Published In

Open biology

DOI

EISSN

2046-2441

ISSN

2046-2441

Publication Date

September 2023

Volume

13

Issue

9

Start / End Page

230122

Related Subject Headings

  • Microtubules
  • Kinesins
  • Cryoelectron Microscopy
  • Cell Division
  • Binding Sites
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 1107 Immunology
  • 0605 Microbiology
  • 0601 Biochemistry and Cell Biology