The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4. - Université Pierre et Marie Curie Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2009

The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.

Résumé

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.

Dates et versions

hal-00416785 , version 1 (15-09-2009)

Identifiants

Citer

Tatiana Isabet, Guillaume Montagnac, Karine Regazzoni, Bertrand Raynal, Fatima El Khadali, et al.. The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.. EMBO Journal, 2009, 28 (18), pp.2687 - 2858. ⟨10.1038/emboj.2009.209⟩. ⟨hal-00416785⟩
151 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More