Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors

How to recruit membrane trafficking machinery PI4KIIIβ is a lipid kinase that underlies Golgi function and is enlisted in biological responses that require rapid delivery of membrane vesicles, such as during the extensive membrane remodeling that occurs at the end of cell division. Burke et al. determined the structure of PI4KIIIβ in a complex with the membrane trafficking GTPase Rab11a. The way in which the proteins interact gives PI4KIIIβ the ability to simultaneously recruit Rab11a and its effectors on specific membranes. Science, this issue p. 1035 A lipid kinase interacts with target membranes, a membrane trafficking guanosine triphosphatase, and its effectors simultaneously. Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)–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 PI4Kβ (PI4KIIIβ) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIβ 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 PI4KIIIβ coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.

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