Present address: Institute for Protein Research, Osaka University, 3-2, Yamadaoka, Suita, Osaka 565–0871, Japan.
Molecular mechanism of ubiquitin recognition by GGA3 GAT domain
Article first published online: 25 MAY 2005
Genes to Cells
Volume 10, Issue 7, pages 639–654, July 2005
How to Cite
Kawasaki, M., Shiba, T., Shiba, Y., Yamaguchi, Y., Matsugaki, N., Igarashi, N., Suzuki, M., Kato, R., Kato, K., Nakayama, K. and Wakatsuki, S. (2005), Molecular mechanism of ubiquitin recognition by GGA3 GAT domain. Genes to Cells, 10: 639–654. doi: 10.1111/j.1365-2443.2005.00865.x
Communicated by: Akihiko Nakano
- Issue published online: 25 MAY 2005
- Article first published online: 25 MAY 2005
- Received: 2 March 2005 Accepted: 25 March 200
GGA (Golgi-localizing, γ-adaptin ear domain homology, ARF-binding) proteins, which constitute a family of clathrin coat adaptor proteins, have recently been shown to be involved in the ubiquitin-dependent sorting of receptors, through the interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1) domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3 C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices α1 and α2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two distinct orientations of ubiquitin Arg42 determine the shape and the charge distribution of ubiquitin Ile44 surface, leading to two different binding modes. Biochemical and NMR data strongly suggest another hydrophobic binding site on C-GAT helices α2 and α3, opposite to the first binding site, also binds ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT domain with higher efficiency in recognizing ubiquitinated receptors for lysosomal receptor degradation.