title: Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits.
abstract: The β1, β2, and β4 subunits of voltage-gated sodium channels reportedly function as cell adhesion molecules. The present crystallographic analysis of the β4 extracellular domain revealed an antiparallel arrangement of the β4 molecules in the crystal lattice. The interface between the two antiparallel β4 molecules is asymmetric, and results in a multimeric assembly. Structure-based mutagenesis and site-directed photo-crosslinking analyses of the β4-mediated cell-cell adhesion revealed that the interface between the antiparallel β4 molecules corresponds to that in the trans homophilic interaction for the multimeric assembly of β4 in cell-cell adhesion. This trans interaction mode is also employed in the β1-mediated cell-cell adhesion. Moreover, the β1 gene mutations associated with generalized epilepsy with febrile seizures plus (GEFS+) impaired the β1-mediated cell-cell adhesion, which should underlie the GEFS+ pathogenesis. Thus, the structural basis for the β-subunit-mediated cell-cell adhesion has been established.
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.|Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.|Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.|Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto 610-0394, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ohsawa
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Shisako
authors.initials: S
authors.lastname: Shoji
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ishizuka-Katsura
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Tosaki
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.|Department of Chemistry and Life Science, Kogakuin University, Hachioji, Tokyo 192-0015, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oyama
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Structural Biology Laboratory, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Center for Life Science Technologies, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Shun-Ichi
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.|Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.|Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto 610-0394, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
authors.affiliation: RIKEN Systems and Structural Biology Center, Tsurumi, Yokohama 230-0045, Japan.|RIKEN Structural Biology Laboratory, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002448:Cell Adhesion; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D000072417:Protein Domains; D062547:Voltage-Gated Sodium Channel beta-1 Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D062585:Voltage-Gated Sodium Channel beta-4 Subunit / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062585:Voltage-Gated Sodium Channel beta-4 Subunit