Structure of the UNC5H2 death domain

Noriko Handa, Mutsuko Kukimoto-Niino, Ryogo Akasaka, Kazutaka Murayama, Takaho Terada, Makoto Inoue, Takashi Yabuki, Masaaki Aoki, Eiko Seki, Takayoshi Matsuda, Emi Nunokawa, Akiko Tanaka, Yoshihide Hayashizaki, Takanori Kigawa, Mikako Shirouzu, Shigeyuki Yokoyama

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


UNC5Hs (UNC5H1-4) are netrin 1 receptors that are involved in axonal guidance and neuronal migration. They are dependence receptors that mediate apoptosis in the absence of netrin 1. UNC5H2-induced apoptosis depends on the interaction of the death domain at the C-terminus with the DAP-kinase death domain and caspase cleavage near the transmembrane region. Here, the crystal structure of the mouse UNC5H2 death domain has been determined at 2.1 Å resolution. The domain adopts a six-helix bundle fold, which is similar to those of the other members of the death-domain superfamily. The UNC5H2 death domain is a dimer in the crystal and in solution. This homodimerized structure may represent the structure of the death domain when netrin 1 binds to the UNC5H2 receptor. Homodimerization of UNC5H2 may block the access of caspase to the cleavage site. In the death-domain dimer, residues in α3 and the 3 10-helix preceding α3 and the residues in α4 make significant contacts, mainly by hydrophobic and van der Waals interactions.

Original languageEnglish
Pages (from-to)1502-1509
Number of pages8
JournalActa Crystallographica Section D: Biological Crystallography
Issue number12
Publication statusPublished - 2006 Dec


  • Apoptosis
  • Death domain
  • Homodimer
  • Netrin 1 receptors
  • Tumour suppressors
  • UNC5H2


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