2e5s
Solution structure of the zf-CCCHx2 domain of muscleblind-like 2, isoform 1 [Homo sapiens]
Structural highlights
FunctionMBNL2_HUMAN Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM).[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. Solution structure of the RNA binding domain in the human muscleblind-like protein 2.,He F, Dang W, Abe C, Tsuda K, Inoue M, Watanabe S, Kobayashi N, Kigawa T, Matsuda T, Yabuki T, Aoki M, Seki E, Harada T, Tomabechi Y, Terada T, Shirouzu M, Tanaka A, Guntert P, Muto Y, Yokoyama S Protein Sci. 2009 Jan;18(1):80-91. PMID:19177353[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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