Structural highlights
Function
[RFIP2_HUMAN] A Rab11 effector protein acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA). Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity.[1] [2] [3] [4]
Publication Abstract from PubMed
The small GTPases Rab11, Rab14 and Rab25 regulate membrane trafficking through the recruitment of Rab11 family-interacting proteins (FIPs) to endocytic compartments. FIPs are multi-domain effector proteins that have a highly conserved Rab-binding domain (RBD) at their C-termini. Several structures of complexes of Rab11 with RBDs have previously been determined, including those of Rab11-FIP2 and Rab11-FIP3. In addition, the structures of the Rab14-FIP1 and Rab25-FIP2 complexes have been determined. All of the RBD structures contain a central parallel coiled coil in the RBD that binds to the switch 1 and switch 2 regions of the Rab. Here, the crystal structure of the uncomplexed RBD of FIP2 is presented at 2.3 A resolution. The structure reveals antiparallel alpha-helices that associate through polar interactions. These include a remarkable stack of arginine residues within a four-helix bundle in the crystal lattice.
Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2.,Kearney AM, Khan AR Acta Crystallogr F Struct Biol Commun. 2020 Aug 1;76(Pt 8):357-363. doi:, 10.1107/S2053230X20009164. Epub 2020 Jul 28. PMID:32744247[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cullis DN, Philip B, Baleja JD, Feig LA. Rab11-FIP2, an adaptor protein connecting cellular components involved in internalization and recycling of epidermal growth factor receptors. J Biol Chem. 2002 Dec 20;277(51):49158-66. Epub 2002 Oct 2. PMID:12364336 doi:10.1074/jbc.M206316200
- ↑ Lindsay AJ, McCaffrey MW. The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane. J Cell Sci. 2004 Sep 1;117(Pt 19):4365-75. Epub 2004 Aug 10. PMID:15304524 doi:10.1242/jcs.01280
- ↑ Ducharme NA, Hales CM, Lapierre LA, Ham AJ, Oztan A, Apodaca G, Goldenring JR. MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells. Mol Biol Cell. 2006 Aug;17(8):3625-37. Epub 2006 Jun 14. PMID:16775013 doi:10.1091/mbc.E05-08-0736
- ↑ Chu BB, Ge L, Xie C, Zhao Y, Miao HH, Wang J, Li BL, Song BL. Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J Biol Chem. 2009 Aug 14;284(33):22481-90. doi: 10.1074/jbc.M109.034355. Epub, 2009 Jun 19. PMID:19542231 doi:10.1074/jbc.M109.034355
- ↑ Kearney AM, Khan AR. Crystal structure of the Rab-binding domain of Rab11 family-interacting protein 2. Acta Crystallogr F Struct Biol Commun. 2020 Aug 1;76(Pt 8):357-363. doi:, 10.1107/S2053230X20009164. Epub 2020 Jul 28. PMID:32744247 doi:http://dx.doi.org/10.1107/S2053230X20009164
