Publication Date:
2014-05-31
Description:
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 PI4Kbeta (PI4KIIIbeta) bound to the small GTPase Rab11a without and with the Rab11 effector protein FIP3. The Rab11-PI4KIIIbeta 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 PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, John E -- Inglis, Alison J -- Perisic, Olga -- Masson, Glenn R -- McLaughlin, Stephen H -- Rutaganira, Florentine -- Shokat, Kevan M -- Williams, Roger L -- MC_U105184308/Medical Research Council/United Kingdom -- PG/11/109/29247/British Heart Foundation/United Kingdom -- PG11/109/29247/British Heart Foundation/United Kingdom -- R01AI099245/AI/NIAID NIH HHS/ -- T32 GM064337/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. jeburke@uvic.ca rlw@mrc-lmb.cam.ac.uk. ; Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. ; Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876499" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Antimalarials/chemistry/pharmacology
;
Binding Sites
;
Cell Line
;
Crystallography, X-Ray
;
Drug Design
;
Humans
;
I-kappa B Kinase/*chemistry
;
Molecular Sequence Data
;
Mutation
;
Phosphotransferases (Alcohol Group Acceptor)/*chemistry/genetics
;
Plasmodium/drug effects/growth & development
;
Protein Binding
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
rab GTP-Binding Proteins/*chemistry
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
