6RIR

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

Summary for 6RIR

• Entry DOI: 10.2210/pdb6rir/pdb
• Descriptor: Ras-related protein Rab-8A, RILP-like protein 2, GUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: membrane trafficking, rab gtpase, effector, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 54037.42

Authors

Waschbusch, D.,Purlyte, E.,Alessi, D.R.,Khan, A.R. (deposition date: 2019-04-25, release date: 2020-01-29, Last modification date: 2024-11-20)

Primary citation

Waschbusch, D.,Purlyte, E.,Pal, P.,McGrath, E.,Alessi, D.R.,Khan, A.R.
Structural Basis for Rab8a Recruitment of RILPL2 via LRRK2 Phosphorylation of Switch 2.
Structure, 28:406-417.e6, 2020

PubMed Abstract: 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 α-helical dimer that bridges two pRab8a molecules. The N termini of the α 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.

PubMed: 32017888
DOI: 10.1016/j.str.2020.01.005

Experimental method

X-RAY DIFFRACTION (1.767 Å)