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1.
Mol Cell ; 42(3): 330-41, 2011 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-21549310

RESUMO

The Polycomb repressive complex 2 (PRC2) confers transcriptional repression through histone H3 lysine 27 trimethylation (H3K27me3). Here, we examined how PRC2 is modulated by histone modifications associated with transcriptionally active chromatin. We provide the molecular basis of histone H3 N terminus recognition by the PRC2 Nurf55-Su(z)12 submodule. Binding of H3 is lost if lysine 4 in H3 is trimethylated. We find that H3K4me3 inhibits PRC2 activity in an allosteric fashion assisted by the Su(z)12 C terminus. In addition to H3K4me3, PRC2 is inhibited by H3K36me2/3 (i.e., both H3K36me2 and H3K36me3). Direct PRC2 inhibition by H3K4me3 and H3K36me2/3 active marks is conserved in humans, mouse, and fly, rendering transcriptionally active chromatin refractory to PRC2 H3K27 trimethylation. While inhibition is present in plant PRC2, it can be modulated through exchange of the Su(z)12 subunit. Inhibition by active chromatin marks, coupled to stimulation by transcriptionally repressive H3K27me3, enables PRC2 to autonomously template repressive H3K27me3 without overwriting active chromatin domains.


Assuntos
Cromatina/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Linhagem Celular , Cromatina/genética , Cristalografia por Raios X , Drosophila , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/química , Humanos , Lisina/química , Metilação , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Complexo Repressor Polycomb 2 , Proteínas do Grupo Polycomb , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteína 4 de Ligação ao Retinoblastoma/química , Proteína 4 de Ligação ao Retinoblastoma/genética , Proteína 4 de Ligação ao Retinoblastoma/metabolismo , Transcrição Gênica
2.
Proteomics ; 7(6): 992-1003, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17370256

RESUMO

The hallmark of a systems biology approach is the integration of computational tools with experimental data encompassing multiple classes of biomolecules across different functional levels. Equally important as the availability of reasonably comprehensive information at the gene, protein, and metabolite levels is the development of adequate analysis and visualization tools to reduce the inherent complexity to interpretable dimensions. In this paper, we describe the integration of a 2-D gel-based proteome map of Staphylococcus aureus Mu50 with genomic and transcriptomic information through a customized data integration and user interface built on the Ensembl genome browser. We illustrate its application and potential through the analysis of a defined system perturbation caused by a mutation in the formyltransferase gene. We envision that this software package, which we called Insieme, can support the development of novel antibiotics by allowing a systems-based view of the bacterial response pathways.


Assuntos
Bactérias/patogenicidade , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteômica , Biologia de Sistemas , Proteínas de Bactérias/genética , Eletroforese em Gel Bidimensional , Análise de Sequência com Séries de Oligonucleotídeos , Proteoma/análise , Proteômica/métodos , Análise de Sequência de Proteína , Software , Staphylococcus aureus
3.
Rapid Commun Mass Spectrom ; 17(16): 1809-14, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12876680

RESUMO

Direct tandem mass spectrometric (MS/MS) analysis of small, singly charged protein ions by tandem time-of-flight mass spectrometry (TOFMS) is demonstrated for proteins up to a molecular mass of 12 kDa. The MALDI-generated singly charged precursor ions predominantly yield product ions resulting from metastable fragmentation at aspartyl and prolyl residues. Additional series of C-terminal sequence ions provide in some cases sufficient information for protein identification. The amount of sample required to obtain good quality spectra is in the high femtomolar to low picomolar range. Within this range, MALDI-MS/MS using TOF/TOF trade mark ion optics now provides the opportunity for direct protein identification and partial characterization without prior enzymatic hydrolysis.


Assuntos
Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Bovinos , Hirudinas/análise , Insulina/análise , Proteínas Recombinantes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Tiorredoxinas/análise
4.
Proteomics ; 2(10): 1445-51, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12422361

RESUMO

In addition to protein identification, characterization of post-translational modifications (PTMs) is an essential task in proteomics. PTMs represent the major reason for the variety of protein isoforms and they can influence protein structure and function. Upon matrix-assisted laser desorption/ionization (MALDI) most post-translationally modified peptides form a fraction of labile molecular ions, which lose PTM-specific residues only after acceleration. Compared to fully accelerated ions these fragment ions are defocused and show in reflector mass spectra reduced resolution. A short time Fourier transform using a Hanning window function now uses this difference in resolution to detect the metastable fragments. Its application over the whole mass range yields frequency distributions and amplitudes as a function of mass, where an increased low frequency proportion is highly indicative for metastable fragments. Applications on the detection of metastable losses originating from carboxamidomethylated cysteines, oxidized methionines, phosphorylated and glycosylated amino acid residues are presented. The metastable loss of mercaptoacetamide detected with this procedure represents a new feature and its integration in search algorithms will improve the specificity of MALDI peptide mass fingerprinting.


Assuntos
Íons , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Algoritmos , Análise de Fourier , Glicopeptídeos/química , Metionina/química , Modelos Estatísticos , Oxigênio/metabolismo , Fosfatos/química , Processamento de Proteína Pós-Traducional , Software
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