title: MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.
abstract: The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.
authors: Laboratory of Structural and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan.
authors: Naoko
authors: N
authors: Iwaya
authors: Hirotoshi
authors: H
authors: Takasu
authors: Natsuko
authors: N
authors: Goda
authors: Masahiro
authors: M
authors: Shirakawa
authors: Toshiki
authors: T
authors: Tanaka
authors: Daizo
authors: D
authors: Hamada
authors: Hidekazu
authors: H
authors: Hiroaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D057146:Multivesicular Bodies; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D058305:Sorting Nexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D010743:Phospholipids; C429023:SNX15 protein, human; D058305:Sorting Nexins; D025262:Vacuolar Proton-Translocating ATPases; D002118:Calcium