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The trihelical bundle subdomain of the GGA proteins interacts with multiple partners through overlapping but distinct sites.

The Golgi-localized, gamma-adaptin ear-containing, ARF-binding (GGA) proteins are monomeric clathrin adaptors that mediate the sorting of cargo at the trans-Golgi network and endosomes. The GGAs contain four different domains named Vps27, Hrs, Stam (VHS); GGAs and TOM1 (GAT); hinge; and gamma-adaptin ear (GAE). The VHS domain recognizes transmembrane cargo, whereas the hinge and GAE regions bind clathrin and accessory proteins, respectively. The GAT domain is a polyfunctional module that interacts with various partners including the small GTPase ARF, the endosomal fusion regulator Rabaptin-5, ubiquitin, and the product of the tumor susceptibility gene 101 (TSG101). Previous x-ray crystallographic analyses showed that the GAT region is composed of two subdomains, an N-terminal helix-loop-helix containing the ARF binding site, and a C-terminal triple alpha-helical (trihelical) bundle. In this study, we define the Rabaptin-5 binding site on the GGA1-GAT domain and its relationship to the binding sites for ubiquitin and TSG101. Our observations show that Rabaptin-5, ubiquitin, and TSG101 bind to overlapping but distinct binding sites on the trihelical bundle. The different GAT binding partners engage in both competitive and cooperative interactions that may be important for the function of the GGAs in protein sorting.

Pubmed ID: 15143060

Authors

  • Mattera R
  • Puertollano R
  • Smith WJ
  • Bonifacino JS

Journal

The Journal of biological chemistry

Publication Data

July 23, 2004

Associated Grants

None

Mesh Terms

  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors
  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Binding Sites
  • Carrier Proteins
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins
  • rab GTP-Binding Proteins