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Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, [gamma]-ear-containing, ADP-ribosylation-factor-binding proteins
- Source :
- Proceedings of the National Academy of Sciences of the United States. Feb 15, 2005, Vol. 102 Issue 7, p2334, 6 p.
- Publication Year :
- 2005
-
Abstract
- The Golgi-localized, [gamma]-ear-containing, Arf (ADP-ribosylation factor)-binding (GGA) proteins are clathrin adaptors that mediate the sorting of transmembrane-cargo molecules at the trans-Golgi network and endosomes. Cargo proteins can be directed into the GGA pathway by at least two different types of sorting signals: acidic cluster-dileucine motifs and covalent modification by ubiquitin. The latter modification is recognized by the GGAs through binding to their GAT [GGA and TOM (target of Myb)] domain. Here we report the crystal structure of the GAT domain of human GGA3 in a 1:1 complex with ubiquitin at 2.8-A resolution. Ubiquitin binds to a hydrophobic and acidic patch on helices [alpha]1 and [alpha]2 of the GAT three-helix bundle that includes Asn-223, Leu-227, Glu-230, Met231, Asp-244, Glu-246, Leu-247, Glu-250, and Leu-251. The GAT-binding surface on ubiquitin is a hydrophobic patch centered on Ile-44 that is also responsible for binding most other ubiquitin effectors. The ubiquitin-binding site observed in the crystal is distinct from the Rabaptin-5-binding site on helices [alpha]2 and [alpha]3 of the GAT domain. Mutational analysis and modeling of the ubiquitin-Rabaptin-5-GAT ternary complex indicates that ubiquitin and Rabaptin-5 can bind to the GAT domain at two different sites without any steric conflict. This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking. protein-protein interactions | structural biology | trafficking
- Subjects :
- Binding proteins -- Research
Proteins -- Research
Science and technology
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 102
- Issue :
- 7
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.129461243