RESUMEN
Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and two tandem WW domains. It is a component of the spliceosomes and interacts with several established splicing factors. Here we demonstrate for the first time that FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing activation function and interaction with the splicing factor SIPP1 (splicing factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW domains of group III. We determined the solution structure of the tandem WW domains of FBP21 and found that the WW domains recognize peptide ligands containing either group II (PPLP) or group III (PPR) motifs. The binding interfaces involve both the XP and XP2 grooves of the two WW domains. Significantly, the tandem WW domains of FBP21 are connected by a highly flexible region, enabling their simultaneous interaction with two proline-rich motifs of SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the conjugation of two low affinity interactions with the tandem WW domains. Our study provides a structural basis for understanding the molecular mechanism underlying the functional implication of FBP21 and the biological specificity of tandem WW domains.
Asunto(s)
Proteínas Portadoras/química , Proteínas Nucleares/química , ARN Mensajero/química , Empalme Alternativo , Secuencia de Aminoácidos , Encéfalo/metabolismo , Proteínas Portadoras/fisiología , ADN Complementario/metabolismo , Regulación de la Expresión Génica , Glutatión Transferasa/metabolismo , Humanos , Isótopos , Modelos Genéticos , Datos de Secuencia Molecular , Proteínas Nucleares/fisiología , Conformación Proteica , Empalme del ARN , Proteínas de Unión al ARN , Proteínas Recombinantes/químicaRESUMEN
SH3 domain binding glutamic acid-rich protein like 3 (SH3BGRL3) is the new member of thioredoxin (TRX) super family, whose posttranslational modified form was identified as tumor necrosis factor alpha (TNF-alpha) inhibitory protein, TIP-B1. In this paper, we determined its solution structure by multi-dimensional nuclear magnetic resonance spectroscopy. The overall structure of human SH3BGRL3 conformed to a TRX-like fold. To understand its function in vivo, the upregulated expression in acute promyelocytic leukemia cell line NB4 at both mRNA and protein level was elucidated. Immunofluorescence and immunohistochemistry staining with monoclonal antibody against SH3BGRL3 demonstrated that it was a cytoplasmic protein in both NB4 cell and human tissues. These results, as a whole, indicate that SH3BGRL3 may function as a regulator in all-trans retinoic acid-induced pathway.
Asunto(s)
Leucemia Promielocítica Aguda/metabolismo , Proteínas Musculares/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cartilla de ADN , ADN Complementario , Humanos , Inmunohistoquímica , Leucemia Promielocítica Aguda/patología , Datos de Secuencia Molecular , Proteínas Musculares/química , Resonancia Magnética Nuclear Biomolecular , Conformación Proteica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: To observe the effect of Fufang Sishen Decoction (FFSSD) on arrhythmia after virus myocarditis. METHODS: One hundred and two cases of arrhythmia after virus myocarditis were randomly divided into two groups. The treatment group was treated with FFSSD, 6 g, b.i.d.; and the control group with propafenone, 150 mg, q 8 h. The therapeutic effects were observed in 4 weeks. RESULTS: The total anti-arrhythmia effects of FFSSD and propafenone were 71.9% and 78.9% respectively (P>0.05). FFSSD took effects relatively slowly with mild and lasting effect. CONCLUSION: The curative effect of FFSSD in treating arrhythmia after virus myocarditis is confirmed. FFSSD has no obvious side effects.