A split active site couples cap recognition by Dcp2 to activation

Floor, Stephen N; Jones, Brittnee N; Hernandez, Gail A; Gross, John D
September 2010
Nature Structural & Molecular Biology;Sep2010, Vol. 17 Issue 9, p1096
Academic Journal
Decapping by Dcp2 is an essential step in 5?-to-3? mRNA decay. In yeast, decapping requires an open-to-closed transition in Dcp2, though the link between closure and catalysis remains elusive. Here we show using NMR that cap binds conserved residues on both the catalytic and regulatory domains of Dcp2. Lesions in the cap-binding site on the regulatory domain reduce the catalytic step by two orders of magnitude and block the formation of the closed state, whereas Dcp1 enhances the catalytic step by a factor of 10 and promotes closure. We conclude that closure occurs during the rate-limiting catalytic step of decapping, juxtaposing the cap-binding region of each domain to form a composite active site. This work suggests a model for regulation of decapping where coactivators trigger decapping by stabilizing a labile composite active site.


Related Articles

  • Structural Basis for Inhibition of the MDM2:p53 Interaction by an Optimized MDM2-Binding Peptide Selected with mRNA Display. Nagata, Takashi; Shirakawa, Kie; Kobayashi, Naohiro; Shiheido, Hirokazu; Tabata, Noriko; Sakuma-Yonemura, Yuko; Horisawa, Kenichi; Katahira, Masato; Doi, Nobuhide; Yanagawa, Hiroshi // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    The oncoprotein MDM2 binds to tumor suppressor protein p53 and inhibits its anticancer activity, which leads to promotion of tumor cell growth and tumor survival. Abrogation of the p53:MDM2 interaction reportedly results in reactivation of the p53 pathway and inhibition of tumor cell...

  • Synergistic effects of acitretin and narrow-band UVB on inducing the expression of heparin-binding epidermal-growth-factor-like growth factor in normal human keratinocytes. Suju Luo; Zhenhui Peng; Yan Zheng; Lukun Zhang; Yiguo Feng; Guorong Wang // Archives of Dermatological Research;Oct2007, Vol. 299 Issue 8, p409 

    It has been reported that heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) plays an important role in regulating keratinocyte growth after retinoic acid treatment. In clinic, there are synergistic effects of retinoic acid plus ultraviolet (UVB) on improving efficacy and...

  • THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation. Tran, Doan D.; Koch, Alexandra; Tamura, Teruko // Cell Communication & Signaling;2014, Vol. 12 Issue 1, p1 

    Cell growth, differentiation, and commitment to a restricted lineage are guided by a timely expressed set of growth factor/cytokine receptors and their down-stream transcription factor genes. Transcriptional control mechanisms of gene expression during differentiation have been mainly studied by...

  • NMR based metabonomics study of NPY Y5 receptor activation in BT-549, a human breast carcinoma cell line. Watanabe, Miki; Sheriff, Sulaiman; Kadeer, Nijiati; Cho, Junho; Lewis, Kenneth; Balasubramaniam, Ambikaipakan; Kennedy, Michael // Metabolomics;Oct2012, Vol. 8 Issue 5, p854 

    Overexpression of neuropeptide Y (NPY) and its receptors has been found in various cancers. In our previous study, we demonstrated expression of NPY Y5 receptor (Y5R) in various breast cancer cell lines along with Y1 receptor. In Y5R expressing BT-549 cells, NPY induced cell proliferation that...

  • Quantification of Uncoupling Protein 2 Reveals Its Main Expression in Immune Cells and Selective Up-Regulation during T-Cell Proliferation. Rupprecht, Anne; Bräuer, Anja U.; Smorodchenko, Alina; Goyn, Justus; Hilse, Karolina E.; Shabalina, Irina G.; Infante-Duarte, Carmen; Pohl, Elena E.; Langmann, Thomas // PLoS ONE;Aug2012, Vol. 7 Issue 8, Special section p1 

    Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein. Although the protein was discovered in 1997, its function and even its tissue distribution are still under debate. Here we present a quantitative analysis of mRNA and protein expression in various mice tissues, revealing...

  • Molecular Pathogenesis of Focal Cortical Dysplasia and Hemimegalencephaly. Crino, Peter B. // Journal of Child Neurology;Apr2005, Vol. 20 Issue 4, p330 

    My laboratory recently demonstrated that there is selective expression of phosphoribosomal S6 protein in balloon cells in focal cortical dysplasia and hemimegalencephaly but no expression of the upstream kinase, phospho-p70S6 kinase. Two proteins activated by phospho-p70S6 kinase, phospho-STAT3...

  • Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA. Marzec, M; Liu, X; Wong, W; Yang, Y; Pasha, T; Kantekure, K; Zhang, P; Woetmann, A; Cheng, M; Odum, N; Wasik, M A // Oncogene;3/17/2011, Vol. 30 Issue 11, p1372 

    The mechanisms of malignant cell transformation mediated by the oncogenic anaplastic lymphoma kinase (ALK) tyrosine kinase remain only partially understood. In this study, we report that T-cell lymphoma (TCL) cells carrying the nucleophosmin (NPM)/ALK fusion protein (ALK+ TCL) strongly express...

  • Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2. Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo // Nucleus (1949-1034);2012, Vol. 3 Issue 1, p29 

    Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance...

  • Role of miR-143 targeting KRAS in colorectal tumorigenesis. Chen, X.; Guo, X.; Zhang, H.; Xiang, Y.; Chen, J.; Yin, Y.; Cai, X.; Wang, K.; Wang, G.; Ba, Y.; Zhu, L.; Wang, J.; Yang, R.; Zhang, Y.; Ren, Z.; Zen, K.; Zhang, J.; Zhang, C.-Y. // Oncogene;3/12/2009, Vol. 28 Issue 10, p1385 

    Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer. By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics