Publication

Article Metrics

Citations


Online attention

Structures of PI4KIIIĀ  complexes show simultaneous recruitment of Rab11 and its effectors

DOI: 10.1126/science.1253397 DOI Help
PMID: 24876499 PMID Help

Authors: John Burke (MRC Laboratory of Molecular Biology, U.K.) , Alison Inglis (MRC Laboratory of Molecular Biology, U.K.) , O. Perisic (Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, U.K.) , Glenn Masson (MRC Laboratory of Molecular Biology, U.K.) , S. H. Mclaughlin (Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, U.K.) , F. Rutaganira (Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, USA.) , K. M. Shokat (Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, USA.) , R. L. Williams (Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, U.K.)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 344 (6187) , PAGES 1035 - 1038

State: Published (Approved)
Published: May 2014
Diamond Proposal Number(s): 8547

Abstract: Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)Ā–containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses. However, the structural basis for coordination of PI4K, GTPases, and their effectors is unknown. Here, we describe structures of PI4K beta (PI4KIII beta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIII beta interface is distinct compared with known structures of Rab complexes and does not involve switch regions used by GTPase effectors. Our data provide a mechanism for how PI4KIII beta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIII beta to combat malaria.

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)