Department of Materials Structure Science, The Graduate University for Advanced Studies* Structural Biology Research Center, PF, IMSS, KEK, Japan** Graduate School of Pharmaceutical Sciences, Kyoto University, Japan***
○Masato Akutsu* Masato Kawasaki** Yohei Katoh*** Ryuichi Kato** Kazuhisa Nakayama*** Soichi Wakatsuki**
Tollip (Toll-interacting protein) was initially identified as a negative regulator of the interleukin1 signaling pathway. Tollip consists of TBD (Tom1 binding domain) at the N-terminal, followed by a C2 domain and a ubiquitin binding CUE (Coupling of ubiquitin conjugation to ER degradation) domain at the C-terminal.
Tollip localizes on the endosomal membrane through the interaction between the C2 domain phosphoinositides. This interaction is thought to play an important role for endosomal trafficking of ubiquitinated proteins.
We have determined the crystal structure of Tollip C2 domain at 2.4Å resolution. The crystal belongs to the hexagonal space group P6522 with cell constants of a = b = 59.3Å and c = 199.1Å. The crystal structure reveals that the Tollip C2 domain is an anti-parallel β-sandwich and belongs to the Type II topology. There is a conventional anion binding site at the concave side of the β-sandwich core, and three basic residues around this site are involved in the interaction with a sulfate ion in the crystal structure. This sulfate binding site is a possible binding site for phosphoinositides.