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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2009-9-17
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1460-2075
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2835-45
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pubmed:dateRevised |
2010-10-11
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pubmed:meshHeading |
pubmed-meshheading:19644450-ADP-Ribosylation Factors,
pubmed-meshheading:19644450-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:19644450-Amino Acid Sequence,
pubmed-meshheading:19644450-Dimerization,
pubmed-meshheading:19644450-Guanosine Triphosphate,
pubmed-meshheading:19644450-Kinesin,
pubmed-meshheading:19644450-Microtubule-Associated Proteins,
pubmed-meshheading:19644450-Models, Biological,
pubmed-meshheading:19644450-Molecular Conformation,
pubmed-meshheading:19644450-Molecular Sequence Data,
pubmed-meshheading:19644450-Mutagenesis, Site-Directed,
pubmed-meshheading:19644450-Protein Binding,
pubmed-meshheading:19644450-Protein Conformation,
pubmed-meshheading:19644450-Protein Structure, Secondary,
pubmed-meshheading:19644450-Protein Structure, Tertiary,
pubmed-meshheading:19644450-Surface Plasmon Resonance
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pubmed:year |
2009
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pubmed:articleTitle |
The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.
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pubmed:affiliation |
Institut Curie, Centre de Recherche, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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