TY - JOUR
T1 - Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors
AU - Burke, John E.
AU - Inglis, Alison J.
AU - Perisic, Olga
AU - Masson, Glenn R.
AU - McLaughlin, Stephen H.
AU - Rutaganira, Florentine
AU - Shokat, Kevan M.
AU - Williams, Roger L.
PY - 2014/5/30
Y1 - 2014/5/30
N2 - 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-enrichedmembranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.
AB - 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-enrichedmembranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIβ to combat malaria.
UR - http://www.scopus.com/inward/record.url?scp=84901624474&partnerID=8YFLogxK
U2 - 10.1126/science.1253397
DO - 10.1126/science.1253397
M3 - Article
C2 - 24876499
AN - SCOPUS:84901624474
SN - 0036-8075
VL - 344
SP - 1035
EP - 1038
JO - Science
JF - Science
IS - 6187
ER -
