title: Characterization of multimetric variants of ubiquitin carboxyl-terminal hydrolase L1 in water by small-angle neutron scattering.
abstract: Here, we illustrated that the morphological structures of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) variants and Parkinson's disease (PD) exhibit good pathological correlation by a small-angle neutron scattering (SANS). UCH-L1 is a neuro-specific multiple functional enzyme, deubiquitinating, ubiquityl ligase, and also involved in stabilization of mono-ubiquitin. To examine the relationship between multiple functions of UCH-L1 and the configuration of its variants [wild-type, I93M (linked to familial Parkinson's disease), and S18Y (linked to reduced risk of Parkinson's disease)], in this report, we proposed that these were all self-assembled dimers by an application of a rotating ellipsoidal model; the configurations of these dimers were quite different. The wild-type was a rotating ellipsoidal. The globular form of the monomeric component deformed by the I93M mutation. Conversely, the S18Y polymorphism promoted the globularity. Thus, the multiple functional balance is closely linked to the intermolecular interactions between the UCH-L1 monomer and the final dimeric configuration.
authors.affiliation: High Energy Accelerator Research Organization, 1-1 Oho, Tsukuba-shi, Ibaraki 305-0801, Japan. sachio@post.kek.jp
authors.forename: Sachio
authors.initials: S
authors.lastname: Naito
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Toru
authors.initials: T
authors.lastname: Yasuda
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Michihiro
authors.initials: M
authors.lastname: Furusaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Adachi
authors.forename: Hirohiko M
authors.initials: HM
authors.lastname: Shimizu
authors.forename: Junichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okada
authors.forename: Kaori
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D033363:Neutron Diffraction; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014867:Water / Q000737:chemistry*
chemical_list: D011994:Recombinant Proteins; C507533:Ubiquitin carboxyl-Terminal Hydrolase L-1, human; D014867:Water; D043222:Ubiquitin Thiolesterase