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Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1

Nature Structural & Molecular Biology volume 11, pages 86–94 (2004)Cite this article

Abstract

Recruitment of the GRIP domain golgins to the trans-Golgi network is mediated by Arl1, a member of the ARF/Arl small GTPase family, through interaction between their GRIP domains and Arl1-GTP. The crystal structure of Arl1-GTP in complex with the GRIP domain of golgin-245 shows that Arl1-GTP interacts with the GRIP domain predominantly in a hydrophobic manner, with the switch II region conferring the main recognition surface. The involvement of the switch and interswitch regions in the interaction between Arl1-GTP and GRIP accounts for the specificity of GRIP domain for Arl1-GTP. Mutations that abolished the Arl1-mediated Golgi localization of GRIP domain golgins have been mapped on the interface between Arl1-GTP and GRIP. Notably, the GRIP domain forms a homodimer in which each subunit interacts separately with one Arl1-GTP. Mutations disrupting the GRIP domain dimerization also abrogated its Golgi targeting, suggesting that the dimeric form of GRIP domain is a functional unit.

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Figure 1: Structure of the Arl1–GRIP complex.
Figure 2: Arl1–GRIP and GRIP–GRIP interfaces.
Figure 3: Sequence alignment of Arls and GRIP domains.
Figure 4: Cellular localization and yeast two-hybrid assays of golgin-245 GRIP domain mutants.
Figure 5: Structural comparisons of Arl1-GTP in the Arl1–GRIP complex with other Arls.
Figure 6: Structural comparisons of the complexes of Arl1–GRIP, ARF1–GAT and Arl2–PDEδ.
Figure 7: Schematic model of recruitment of Golgin-245 to the Golgi membrane by Arl1.

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Acknowledgements

We thank P. Tucker at BW7A (European Molecular Biology Laboratory, Hamburg, Germany) for assistance and access to synchrotron radiation facilities, and M.J. Fritzler and E.K.L. Chan for providing the full-length cDNA of human golgin-97. This work is financially supported by the Agency for Science, Technology and Research (A*STAR) in Singapore (to W.H. and H.S.).

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  1. Mousheng Wu and Lei Lu: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, 30 Medical Drive, 117609, Singapore

    Mousheng Wu & Haiwei Song

  2. Laboratory of Membrane Biology, Institute of Molecular and Cell Biology, 30 Medical Drive, 117609, Singapore

    Lei Lu & Wanjin Hong

  3. Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, 117543, Singapore

    Mousheng Wu & Haiwei Song

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Correspondence to Wanjin Hong or Haiwei Song.

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Wu, M., Lu, L., Hong, W. et al. Structural basis for recruitment of GRIP domain golgin-245 by small GTPase Arl1. Nat Struct Mol Biol 11, 86–94 (2004). https://doi.org/10.1038/nsmb714

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