6rir

Crystal structure of phosphorylated Rab8a in complex with the Rab-binding domain of RILPL2

spinqualitylabelsall models 6rir, resolution 1.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rir is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.767Å Ligands: GOL, GTP, MG, TPO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RAB8A_HUMAN May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B and RAB11A participates in epithelial cell polarization. Publication Abstract from PubMed Rab8a is associated with the dynamic regulation of membrane protrusions in polarized cells. Rab8a is one of several Rab GTPases that are substrates of leucine-rich repeat kinase 2 (LRRK2), a serine/threonine kinase that is linked to Parkinson's disease. Rab8a is phosphorylated at T72 (pT72) in its switch 2 helix and recruits the phospho-specific effector RILPL2, which subsequently regulates ciliogenesis. Here, we report the crystal structure of phospho-Rab8a (pRab8a) in complex with the RH2 (RILP homology) domain of RILPL2. The complex is a heterotetramer with RILPL2 forming a central alpha-helical dimer that bridges two pRab8a molecules. The N termini of the alpha helices cross over, forming an X-shaped cap (X-cap) that orients Arg residues from RILPL2 toward pT72. X-cap residues critical for pRab8a binding are conserved in JIP3 and JIP4, which also interact with LRRK2-phosphorylated Rab10. We propose a general mode of recognition for phosphorylated Rab GTPases by this family of phospho-specific effectors. Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2.,Waschbusch D, Purlyte E, Pal P, McGrath E, Alessi DR, Khan AR Structure. 2020 Feb 1. pii: S0969-2126(20)30005-8. doi:, 10.1016/j.str.2020.01.005. PMID:32017888 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ras-related protein Rab 3D structures

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