4d0m

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Phosphatidylinositol 4-kinase III beta in a complex with Rab11a-GTP- gamma-S and the Rab-binding domain of FIP3Phosphatidylinositol 4-kinase III beta in a complex with Rab11a-GTP- gamma-S and the Rab-binding domain of FIP3

Structural highlights

4d0m is a 36 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 6Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PI4KB_HUMAN Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity).[1] [2] [3]

Publication Abstract from PubMed

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.

Structures of PI4KIIIbeta complexes show simultaneous recruitment of Rab11 and its effectors.,Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397. PMID:24876499[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Suzuki K, Hirano H, Okutomi K, Suzuki M, Kuga Y, Fujiwara T, Kanemoto N, Isono K, Horie M. Identification and characterization of a novel human phosphatidylinositol 4-kinase. DNA Res. 1997 Aug 31;4(4):273-80. PMID:9405935
  2. ↑ Godi A, Pertile P, Meyers R, Marra P, Di Tullio G, Iurisci C, Luini A, Corda D, De Matteis MA. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol. 1999 Sep;1(5):280-7. PMID:10559940 doi:http://dx.doi.org/10.1038/12993
  3. ↑ Heilmeyer LM Jr, Vereb G Jr, Vereb G, Kakuk A, Szivak I. Mammalian phosphatidylinositol 4-kinases. IUBMB Life. 2003 Feb;55(2):59-65. PMID:12749687 doi:http://dx.doi.org/10.1002/tbmb.718540873
  4. ↑ Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL. Structures of PI4KIIIbeta complexes show simultaneous recruitment of Rab11 and its effectors. Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397. PMID:24876499 doi:http://dx.doi.org/10.1126/science.1253397

4d0m, resolution 6.00Å

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