2DWX

Co-crystal Structure Analysis of GGA1-GAE with the WNSF motif

Summary for 2DWX

• Entry DOI: 10.2210/pdb2dwx/pdb
• Related: 2dwy
• Descriptor: ADP-ribosylation factor-binding protein GGA1, hinge peptide from ADP-ribosylation factor binding protein GGA1 (3 entities in total)
• Functional Keywords: ig fold, adaptin, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Golgi apparatus, trans-Golgi network membrane; Peripheral membrane protein: Q9UJY5 Q9UJY5
• Total number of polymer chains: 6
• Total formula weight: 62336.07

Authors

Inoue, M.,Shiba, T.,Yamada, Y.,Ihara, K.,Kawasaki, M.,Kato, R.,Nakayama, K.,Wakatsuki, S. (deposition date: 2006-08-21, release date: 2007-04-17, Last modification date: 2023-10-25)

Primary citation

Inoue, M.,Shiba, T.,Ihara, K.,Yamada, Y.,Hirano, S.,Kamikubo, H.,Kataoka, M.,Kawasaki, M.,Kato, R.,Nakayama, K.,Wakatsuki, S.
Molecular Basis for Autoregulatory Interaction Between GAE Domain and Hinge Region of GGA1
Traffic, 8:904-913, 2007

PubMed Abstract: Golgi-localizing, gamma-adaptin ear domain homology, ADP ribosylation factor-binding (GGA) proteins and the adaptor protein (AP) complex, AP-1, are involved in membrane traffic between the trans Golgi network and the endosomes. The gamma-adaptin ear (GAE) domain of GGAs and the gamma1 ear domain of AP-1 interact with an acidic phenylalanine motif found in accessory proteins. The GAE domain of GGA1 (GGA1-GAE) interacts with a WNSF-containing peptide derived from its own hinge region, although the peptide sequence deviates from the standard acidic phenylalanine motif. We report here the structure of GGA1-GAE in complex with the GGA1 hinge peptide, which revealed that the two aromatic side chains of the WNSF sequence fit into a hydrophobic groove formed by aliphatic portions of the side chains of conserved arginine and lysine residues of GGA1-GAE, in a similar manner to the interaction between GGA-GAEs and acidic phenylalanine sequences from the accessory proteins. Fluorescence quenching experiments indicate that the GGA1 hinge region binds to GGA1-GAE and competes with accessory proteins for binding. Taken together with the previous observation that gamma1 ear binds to the GGA1 hinge region, the interaction between the hinge region and the GAE domain underlies the autoregulation of GGA function in clathrin-mediated trafficking through competing with the accessory proteins and the AP-1 complex.

PubMed: 17506864
DOI: 10.1111/j.1600-0854.2007.00577.x

Experimental method

X-RAY DIFFRACTION (2.55 Å)