title: Structure of the UNC5H2 death domain.
abstract: 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 A 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 alpha3 and the 3(10)-helix preceding alpha3 and the residues in alpha4 make significant contacts, mainly by hydrophobic and van der Waals interactions.
authors.affiliation: RIKEN Genomic Sciences Center, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Handa
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Kukimoto-Niino
authors.forename: Ryogo
authors.initials: R
authors.lastname: Akasaka
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Murayama
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Yabuki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Aoki
authors.forename: Eiko
authors.initials: E
authors.lastname: Seki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Emi
authors.initials: E
authors.lastname: Nunokawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019281:Dimerization; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry; D000075386:Netrin Receptors; D000075388:Netrin-1; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry*; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000737:chemistry
chemical_list: D009414:Nerve Growth Factors; D000075386:Netrin Receptors; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C000617353:Ntn1 protein, mouse; C000617308:Unc5A protein, mouse; C000617307:Unc5b protein, mouse