Structural highlights
Function
[KI13B_HUMAN] Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes.[1] [ADAP1_HUMAN] GTPase-activating protein for the ADP ribosylation factor family (Probable). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4).[2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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 alpha1 (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.
Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin {alpha}1.,Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, Mackenzie F, Chishti AH, Park HW Proc Natl Acad Sci U S A. 2010 Nov 5. PMID:21057110[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yoshimura Y, Terabayashi T, Miki H. Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation. Mol Cell Biol. 2010 May;30(9):2206-19. doi: 10.1128/MCB.01181-09. Epub 2010 Mar, 1. PMID:20194617 doi:10.1128/MCB.01181-09
- ↑ Venkateswarlu K, Cullen PJ. Molecular cloning and functional characterization of a human homologue of centaurin-alpha. Biochem Biophys Res Commun. 1999 Aug 19;262(1):237-44. PMID:10448098 doi:10.1006/bbrc.1999.1065
- ↑ Venkateswarlu K, Oatey PB, Tavare JM, Jackson TR, Cullen PJ. Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1. Biochem J. 1999 Jun 1;340 ( Pt 2):359-63. PMID:10333475
- ↑ Tong Y, Tempel W, Wang H, Yamada K, Shen L, Senisterra GA, Mackenzie F, Chishti AH, Park HW. Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin {alpha}1. Proc Natl Acad Sci U S A. 2010 Nov 5. PMID:21057110 doi:10.1073/pnas.1009008107
