Structural highlights
Function
ARF6_HUMAN GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in the regulation of dendritic spine development (By similarity). Contributes to the regulation of dendritic branching and filopodia extension.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The JNK-interacting proteins, JIP3 and JIP4, are specific effectors of the small GTP-binding protein ARF6. The interaction of ARF6-GTP with the second leucine zipper (LZII) domains of JIP3/JIP4 regulates the binding of JIPs to kinesin-1 and dynactin. Here, we report the crystal structure of ARF6-GTP bound to the JIP4-LZII at 1.9 A resolution. The complex is a heterotetramer with dyad symmetry arranged in an ARF6-(JIP4)(2)-ARF6 configuration. Comparison of the ARF6-JIP4 interface with the equivalent region of ARF1 shows the structural basis of JIP4's specificity for ARF6. Using site-directed mutagenesis and surface plasmon resonance, we further show that non-conserved residues at the switch region borders are the key structural determinants of JIP4 specificity. A structure-derived model of the association of the ARF6-JIP3/JIP4 complex with membranes shows that the JIP4-LZII coiled-coil should lie along the membrane to prevent steric hindrances, resulting in only one ARF6 molecule bound. Such a heterotrimeric complex gives insights to better understand the ARF6-mediated motor switch regulatory function.
The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.,Isabet T, Montagnac G, Regazzoni K, Raynal B, El Khadali F, England P, Franco M, Chavrier P, Houdusse A, Menetrey J EMBO J. 2009 Sep 16;28(18):2835-45. Epub 2009 Jul 30. PMID:19644450[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ D'Souza-Schorey C, Stahl PD. Myristoylation is required for the intracellular localization and endocytic function of ARF6. Exp Cell Res. 1995 Nov;221(1):153-9. PMID:7589240 doi:http://dx.doi.org/10.1006/excr.1995.1362
- ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
- ↑ Pasqualato S, Menetrey J, Franco M, Cherfils J. The structural GDP/GTP cycle of human Arf6. EMBO Rep. 2001 Mar;2(3):234-8. PMID:11266366 doi:10.1093/embo-reports/kve043
- ↑ Isabet T, Montagnac G, Regazzoni K, Raynal B, El Khadali F, England P, Franco M, Chavrier P, Houdusse A, Menetrey J. The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4. EMBO J. 2009 Sep 16;28(18):2835-45. Epub 2009 Jul 30. PMID:19644450 doi:10.1038/emboj.2009.209
