Molecular basis for autoregulatory interaction between GAE domain and hinge region of GGA1

Michio Inoue, Tomoo Shiba, Kentaro Ihara, Yusuke Yamada, Satoshi Hirano, Hironari Kamikubo, Mikio Kataoka, Masato Kawasaki, Ryuichi Kato, Kazuhisa Nakayama, Soichi Wakatsuki

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Golgi-localizing, γ-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 γ-adaptin ear (GAE) domain of GGAs and the γ1 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 γ1 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.

Original languageEnglish
Pages (from-to)904-913
Number of pages10
JournalTraffic
Volume8
Issue number7
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • AP-1
  • Autoregulation
  • Clathrin adaptors
  • Crystal structure
  • GGA
  • γ-adaptin ear

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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