Mechanochemical tuning of a kinesin motor essential for malaria parasite transmission.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 11 2022
16 11 2022
Historique:
received:
28
01
2022
accepted:
02
11
2022
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
22
11
2022
Statut:
epublish
Résumé
Plasmodium species cause malaria and kill hundreds of thousands annually. The microtubule-based motor kinesin-8B is required for development of the flagellated Plasmodium male gamete, 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 kinesin-8B motor domains from P. berghei and P. falciparum. Both motors drive ATP-dependent microtubule gliding, but also catalyse ATP-dependent microtubule depolymerisation. We determined these motors' microtubule-bound structures using cryo-electron microscopy, which showed very similar modes 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 required for motility and depolymerisation activities of these motors. These data suggest that the mechanochemistry of Plasmodium kinesin-8Bs is functionally tuned to support flagella formation.
Identifiants
pubmed: 36384964
doi: 10.1038/s41467-022-34710-x
pii: 10.1038/s41467-022-34710-x
pmc: PMC9669022
doi:
Substances chimiques
Kinesins
EC 3.6.4.4
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6988Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N017609/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T016124.1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N018176/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217186/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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