title: Crystal structure of human importin-α1 (Rch1), revealing a potential autoinhibition mode involving homodimerization.
abstract: In this study, we determined the crystal structure of N-terminal importin-β-binding domain (IBB)-truncated human importin-α1 (ΔIBB-h-importin-α1) at 2.63 Å resolution. The crystal structure of ΔIBB-h-importin-α1 reveals a novel closed homodimer. The homodimer exists in an autoinhibited state in which both the major and minor nuclear localization signal (NLS) binding sites are completely buried in the homodimerization interface, an arrangement that restricts NLS binding. Analytical ultracentrifugation studies revealed that ΔIBB-h-importin-α1 is in equilibrium between monomers and dimers and that NLS peptides shifted the equilibrium toward the monomer side. This finding suggests that the NLS binding sites are also involved in the dimer interface in solution. These results show that when the IBB domain dissociates from the internal NLS binding sites, e.g., by binding to importin-β, homodimerization possibly occurs as an autoinhibition state.
authors: Global Research Cluster Collaboration Promotion Unit, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors: Hideyuki
authors: H
authors: Miyatake
authors: Protein Wave Corporation, 1-16-5 Nishitomigaoka, Nara 631-0006, Japan.
authors: Akira
authors: A
authors: Sanjoh
authors: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors: Satoru
authors: S
authors: Unzai
authors: Viral Infectious Diseases Unit, RIKEN, 2-1, Hirosawa, Wako-shi 351-0198, Japan.
authors: Go
authors: G
authors: Matsuda
authors: Protein Wave Corporation, 1-16-5 Nishitomigaoka, Nara 631-0006, Japan.
authors: Yuko
authors: Y
authors: Tatsumi
authors: Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Building 76 Level 2, Wellington Road, Clayton VIC 3800, Australia; Laboratory of Nuclear Transport Dynamics, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki-shi, Osaka 567-0085, Japan.
authors: Yoichi
authors: Y
authors: Miyamoto
authors: Global Research Cluster Collaboration Promotion Unit, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors: Naoshi
authors: N
authors: Dohmae
authors: Viral Infectious Diseases Unit, RIKEN, 2-1, Hirosawa, Wako-shi 351-0198, Japan.
authors: Yoko
authors: Y
authors: Aida
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D028901:alpha Karyopherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D028901:alpha Karyopherins; C087978:karyopherin alpha 2