title: Solution structure of the RNA binding domain in the human muscleblind-like protein 2.
abstract: The muscleblind-like (MBNL) proteins 1, 2, and 3, which contain four CCCH zinc finger motifs (ZF1-4), are involved in the differentiation of muscle inclusion by controlling the splicing patterns of several pre-mRNAs. Especially, MBNL1 plays a crucial role in myotonic dystrophy. The CCCH zinc finger is a sequence motif found in many RNA binding proteins and is suggested to play an important role in the recognition of RNA molecules. Here, we solved the solution structures of both tandem zinc finger (TZF) motifs, TZF12 (comprising ZF1 and ZF2) and TZF34 (ZF3 and ZF4), in MBNL2 from Homo sapiens. In TZF12 of MBNL2, ZF1 and ZF2 adopt a similar fold, as reported previously for the CCCH-type zinc fingers in the TIS11d protein. The linker between ZF1 and ZF2 in MBNL2 forms an antiparallel beta-sheet with the N-terminal extension of ZF1. Furthermore, ZF1 and ZF2 in MBNL2 interact with each other through hydrophobic interactions. Consequently, TZF12 forms a single, compact global fold, where ZF1 and ZF2 are approximately symmetrical about the C2 axis. The structure of the second tandem zinc finger (TZF34) in MBNL2 is similar to that of TZF12. This novel three-dimensional structure of the TZF domains in MBNL2 provides a basis for functional studies of the CCCH-type zinc finger motifs in the MBNL protein family.
authors.affiliation: RIKEN Systems and Structural Biology Center, Yokohama 230-0045, Japan.
authors.forename: Fahu
authors.initials: F
authors.lastname: He
authors.forename: Weirong
authors.initials: W
authors.lastname: Dang
authors.forename: Chikage
authors.initials: C
authors.lastname: Abe
authors.forename: Kengo
authors.initials: K
authors.lastname: Tsuda
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Satoru
authors.initials: S
authors.lastname: Watanabe
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Takanori
authors.initials: T
authors.lastname: Kigawa
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Matsuda
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: Takushi
authors.initials: T
authors.lastname: Harada
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tomabechi
authors.forename: Takaho
authors.initials: T
authors.lastname: Terada
authors.forename: Mikako
authors.initials: M
authors.lastname: Shirouzu
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Peter
authors.initials: P
authors.lastname: Güntert
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Muto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D016335:Zinc Fingers
chemical_list: C499444:MBNL2 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins