3LJU

Crystal structure of full length centaurin alpha-1 bound with the head group of PIP3

Summary for 3LJU

• Entry DOI: 10.2210/pdb3lju/pdb
• Descriptor: Arf-GAP with dual PH domain-containing protein 1, ZINC ION, (2R)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane -1,2-diyl dioctanoate, ... (4 entities in total)
• Functional Keywords: structural genomics consortium, gap, gtpase activation, sgc, metal-binding, nucleus, phosphoprotein, zinc-finger, hydrolase activator
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O75689
• Total number of polymer chains: 1
• Total formula weight: 46718.28

Authors

Shen, L.,Tong, Y.,Tempel, W.,MacKenzie, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Weigelt, J.,Bochkarev, A.,Park, H.,Structural Genomics Consortium (SGC) (deposition date: 2010-01-26, release date: 2010-11-24, Last modification date: 2023-09-06)

Primary citation

Tong, Y.,Tempel, W.,Wang, H.,Yamada, K.,Shen, L.,Senisterra, G.A.,MacKenzie, F.,Chishti, A.H.,Park, H.W.
Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin alpha1.
Proc.Natl.Acad.Sci.USA, 107:20346-20351, 2010

PubMed Abstract: 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.

PubMed: 21057110
DOI: 10.1073/pnas.1009008107

Experimental method

X-RAY DIFFRACTION (1.702 Å)