Article
- The EMBO Journal (2004) 23, 3909 - 3917
- doi:10.1038/sj.emboj.7600411
Published online: 30 September 2004
Subject Categories:
Crystal structure of human GGA1 GAT domain complexed with the GAT-binding domain of Rabaptin5
Guangyu Zhu1,a, Peng Zhai1,a, Xiangyuan He2, Nancy Wakeham1, Karla Rodgers3, Guangpu Li3, Jordan Tang2,3 and Xuejun C Zhang1
- Crystallography Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
- Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
- Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Correspondence to:
Xuejun C Zhang, Crystallography Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA. Tel.: +1 405 271 7402; Fax: +1 405 271 7953; E-mail: zhangc@omrf.ouhsc.edu
aThese authors contributed equally to this work
Received 21 June 2004; Accepted 19 August 2004
Abstract
GGA proteins coordinate the intracellular trafficking of clathrin-coated vesicles through their interaction with several other proteins. The GAT domain of GGA proteins interacts with ARF, ubiquitin, and Rabaptin5. The GGA–Rabaptin5 interaction is believed to function in the fusion of trans-Golgi-derived vesicles to endosomes. We determined the crystal structure of a human GGA1 GAT domain fragment in complex with the Rabaptin5 GAT-binding domain. In this structure, the Rabaptin5 domain is a 90-residue-long helix. At the N-terminal end, it forms a parallel coiled-coil homodimer, which binds one GAT domain of GGA1. In the C-terminal region, it further assembles into a four-helix bundle tetramer. The Rabaptin5-binding motif of the GGA1 GAT domain consists of a three-helix bundle. Thus, the binding between Rabaptin5 and GGA1 GAT domain is based on a helix bundle–helix bundle interaction. The current structural observation is consistent with previously reported mutagenesis data, and its biological relevance is further confirmed by new mutagenesis studies and affinity analysis. The four-helix bundle structure of Rabaptin5 suggests a functional role in tethering organelles.
Keywords:
- crystal structure,
- GAT domain,
- GGA proteins,
- intracellular trafficking,
- Rabaptin5
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