PXD037474

PXD037474 is an original dataset announced via ProteomeXchange.

Title	Mechanochemical tuning of a kinesin motor essential for malaria parasite transmission
Description	Kinesins are a superfamily of molecular motors that undertake ATP-dependent microtubule-based movement or regulate microtubule dynamics. Plasmodium species, which cause malaria and kill hundreds of thousands annually, encode ~9 kinesins in their genomes. Of these, two – kinesin-8B and kinesin-8X - are canonically classified as kinesin-8s, which in other eukaryotes typically modulate microtubule dynamics. Unexpectedly, Plasmodium kinesin-8B is required for development of the flagellated male gamete in the mosquito host, and its absence completely blocks parasite transmission. To understand the molecular basis of kinesin-8B’s essential role, we characterised the in vitro properties of the kinesin-8B motor domains from P. berghei and P. falciparum. Both motors drive plus-end directed ATP-dependent microtubule gliding, but also catalyse ATP-dependent microtubule depolymerisation. We determined the microtubule-bound structures of these motors using cryo-electron microscopy. P. berghei and P. falciparum kinesin-8B exhibit a very similar mode of microtubule interaction, in which Plasmodium-distinct sequences at the microtubule-kinesin interface influence motor function. Intriguingly, however, P. berghei kinesin-8B exhibits a non-canonical structural response to ATP analogue binding such that neck linker docking is not induced. Nevertheless, the neck linker region is absolutely required for motility and depolymerisation activities of these motors. Taken together, these data suggest that the mechanochemistry of Plasmodium kinesin-8Bs has been functionally tuned to efficiently contribute to flagella formation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:47.206.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD037474
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andrew Bottrill
SpeciesList	scientific name: Plasmodium berghei ANKA; NCBI TaxID: 5823;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-17 01:12:55	ID requested
1	2022-12-05 06:33:08	announced
⏵ 2	2023-11-14 08:24:48	announced	2023-11-14: Updated project metadata.

Liu T, Shilliday F, Cook AD, Zeeshan M, Brady D, Tewari R, Sutherland CJ, Roberts AJ, Moores CA, Mechanochemical tuning of a kinesin motor essential for malaria parasite transmission. Nat Commun, 13(1):6988(2022) [pubmed]

10.6019/PXD037474;

submitter keyword: cryo-EM, malaria, microtubule, Warwick_RTP,ATPase, kinesin, motor, flagella

Carolyn A. Moores
contact affiliation	Institute of Structural and Molecular Biology, Birkbeck College, London WC1E 7HX, UK
contact email	c.moores@bbk.ac.uk
lab head
Andrew Bottrill
contact affiliation	University of Warwick
contact email	a.r.bottrill@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/12/PXD037474

PRIDE project URI

• PRIDE
  1. PXD037474
     1. Label: PRIDE project
     2. Name: Mechanochemical tuning of a kinesin motor essential for malaria parasite transmission