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Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin α1
journal contributionposted on 2022-11-18, 21:53 authored by Yufeng Tong, Wolfram Tempel, Hui Wang, Kaori YamadaKaori Yamada, Limin Shen, Guillermo A Senisterra, Farrell MacKenzie, Athar H Chishti, Hee-Won Park
Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P(2)). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.
Cytoskeletal Interaction of Human Dlg Protein | Funder: National Institutes of Health (National Cancer Institute) | Grant ID: R01CA094414
CitationTong, Y., Tempel, W., Wang, H., Yamada, K., Shen, L., Senisterra, G. A., MacKenzie, F., Chishti, A. H.Park, H. -W. (2010). Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin α1. Proceedings of the National Academy of Sciences of the United States of America, 107(47), 20346-20351. https://doi.org/10.1073/pnas.1009008107
PublisherProceedings of the National Academy of Sciences
CategoriesNo categories selected
1.1 Normal biological development and functioningGeneric health relevancekinesinforkhead-associated domainvesicle transportphosphatidylinositol triphosphateneuronal developmentAdaptor Proteins, Signal TransducingAxonsBiological TransportCalorimetryChromatography, AffinityChromatography, GelCloning, MolecularComputational BiologyCrystallographyElectrophoresis, Polyacrylamide GelGlutathione TransferaseHumansKinesinsModels, ChemicalModels, MolecularMutagenesis, Site-DirectedNerve Tissue ProteinsNeuronsPhosphatidylinositol PhosphatesProtein ConformationTransport VesiclesKinesin