Ubiquitin Binding: GAT Domain

The GAT domain of human GGA1.

Domain Binding and Function

GGA and Tom1 (GAT) domains interact with GTP-bound ARF and are crucial for membrane recruitment of GGAs to the trans-Golgi network. The N-terminal subdomain is important for GAT binding to GTP-bound ARF as the C-terminal subdomain can bind to ubiquitin. The binding of the GAT domain to ubiquitin can be enhanced by the presence of GTP-bound ARF. The GAT domain has structural homology to the SNARE family that contains the same type of three-helix bundle, implicating a role of the GAT domain in membrane fusion. Although GGA1 and GGA3 interact with ARF-GTP and ubiquitin, the functions of GAT in GGA2 and Tom1 are still unclear.

Structure

The N-GAT subdomain or hook subdomain comprises of a helix-loop-helix structure where the N-terminal half of the second long helix α1 is responsible for ARF binding. The C-GAT subdomain constitutes a 3-helix bundle composed of the C-terminal half of α1, α2 and α3. Binding of ubiquitin is mediated by the interaction between residues on one side of α3 helix of the GAT domain and the Ile-44 surface patch of ubiquitin.

Structure Reference

  1. Suer, S. et al. (2003) PNAS 100(8), 4451–4456.
  2. Shiba, T. et al. (2003) Nat. Struc. Biol. 10(5), 386–392.
  3. Shiba, Y. et al. (2004) JBC 279(8), 7105–7111.

Examples of Domain Proteins

Ubiquitin Binding: GAT Domain

Binding Examples

GAT Domain Proteins Binding Partners
GGA1 ARF1
GGA2 ARF3
GGA3 Rabaptin-5
Tom1