2W83

Crystal structure of the ARF6 GTPase in complex with a specific effector, JIP4

Summary for 2W83

• Entry DOI: 10.2210/pdb2w83/pdb
• Related: 1E0S 2A5D 2A5F 2A5G 2J5X
• Descriptor: ADP-RIBOSYLATION FACTOR 6, C-JUN-AMINO-TERMINAL KINASE-INTERACTING PROTEIN 4, GUANOSINE-5'-TRIPHOSPHATE, ... (7 entities in total)
• Functional Keywords: golgi apparatus, protein transport, er-golgi transport, arf, gtpase, effector, myristate, cytoplasm, nucleotide-binding, alternative splicing, gtp-binding, phosphoprotein, heterotetramer, transport, coiled-coil, lipoprotein, coiled coil
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Golgi apparatus: P62330; Cytoplasm. Isoform 5: Cytoplasmic vesicle, secretory vesicle, acrosome: 2W83
• Total number of polymer chains: 5
• Total formula weight: 76991.96

Authors

Isabet, T.,Montagnac, G.,Regazzoni, K.,Raynal, B.,El Khadali, F.,Franco, M.,England, P.,Chavrier, P.,Houdusse, A.,Menetrey, J. (deposition date: 2009-01-08, release date: 2009-07-14, Last modification date: 2023-12-13)

Primary citation

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., 28:2835-, 2009

PubMed Abstract: 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.

PubMed: 19644450
DOI: 10.1038/EMBOJ.2009.209

Experimental method

X-RAY DIFFRACTION (1.93 Å)