Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Biochemistry ; 48(45): 10724-32, 2009 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-19824649

RESUMO

The overall morphology and Cu(II) ion coordination for the aggregated amyloid-beta(1-40) [Abeta(1-40)] in N-ethylmorpholine (NEM) buffer are affected by Cu(II) ion concentration. This effect is investigated by transmission electron microscopy (TEM), atomic force microscopy (AFM), and electron spin echo envelope modulation (ESEEM) spectroscopy. At lower than equimolar concentrations of Cu(II) ions, fibrillar aggregates of Abeta(1-40) are observed. At these concentrations of Cu(II), the monomeric and fibrillar Abeta(1-40) ESEEM data indicate that the Cu(II) ion is coordinated by histidine residues. For aggregated Abeta(1-40) at a Cu(II):Abeta molar ratio of 2:1, TEM and AFM images show both linear fibrils and granular amorphous aggregates. The ESEEM spectra show that the multi-histidine coordination for Cu(II) ion partially breaks up and becomes exposed to water or exchangeable protons of the peptide at a higher Cu(II) concentration. Since the continuous-wave electron spin resonance results also suggest two copper-binding sites in Abeta(1-40), the proton ESEEM peak may arise from the second copper-binding site, which may be significantly involved in the formation of granular amorphous aggregates. Thioflavin T fluorescence and circular dichroism experiments also show that Cu(II) inhibits the formation of fibrils and induces a nonfibrillar beta-sheet conformation. Therefore, we propose that Abeta(1-40) has a second copper-binding site in a proton-rich environment and the second binding Cu(II) ion interferes with a conformational transition into amyloid fibrils, inducing the formation of granular amorphous aggregates.


Assuntos
Peptídeos beta-Amiloides/química , Cobre/metabolismo , Fragmentos de Peptídeos/química , Sequência de Aminoácidos , Sítios de Ligação , Espectroscopia de Ressonância de Spin Eletrônica , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Prótons , Análise Espectral/métodos
2.
Cell ; 113(3): 369-81, 2003 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-12732144

RESUMO

Chaperonins use ATPase cycling to promote conformational changes leading to protein folding. The prokaryotic chaperonin GroEL requires a cofactor, GroES, which serves as a "lid" enclosing substrates in the central cavity and confers an asymmetry on GroEL required for cooperative transitions driving the reaction. The eukaryotic chaperonin TRiC/CCT does not have such a cofactor but appears to have a "built-in" lid. Whether this seemingly symmetric chaperonin also operates through an asymmetric cycle is unclear. We show that unlike GroEL, TRiC does not close its lid upon nucleotide binding, but instead responds to the trigonal-bipyramidal transition state of ATP hydrolysis. Further, nucleotide analogs inducing this transition state confer an asymmetric conformation on TRiC. Similar to GroEL, lid closure in TRiC confines the substrates in the cavity and is essential for folding. Understanding the distinct mechanisms governing eukaryotic and bacterial chaperonin function may reveal how TRiC has evolved to fold specific eukaryotic proteins.


Assuntos
Trifosfato de Adenosina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Adenosina Trifosfatases/metabolismo , Animais , Sítios de Ligação , Bovinos , Hidrólise , Modelos Moleculares , Conformação Proteica , Dobramento de Proteína , Relação Estrutura-Atividade , Ubiquitina-Proteína Ligases , Difração de Raios X , Região do Complexo-t do Genoma
3.
J Proteome Res ; 1(4): 307-15, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12645886

RESUMO

Yersinia pestis capsular antigen Caf1 is shown to be a beta-structural protein that in polymeric form possesses very high conformational stability. Different approaches show that a dimer is the minimal cooperative block of Caf1 adhesin. Caf1 dimer interacts effectively with IL-1 receptors of human macrophage and epithelial cells. The specificity of such interaction is confirmed by the inhibition of IL-1alpha binding by Caf1. The Caf1 role in pneumonic plague pathogenesis is discussed.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Peste/microbiologia , Yersinia pestis/imunologia , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Cápsulas Bacterianas/química , Cápsulas Bacterianas/imunologia , Cápsulas Bacterianas/metabolismo , Linhagem Celular , Dicroísmo Circular , Dimerização , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Guanidina/química , Humanos , Concentração de Íons de Hidrogênio , Macrófagos/citologia , Macrófagos/metabolismo , Modelos Biológicos , Peste/imunologia , Peste/metabolismo , Ligação Proteica , Conformação Proteica , Desnaturação Proteica , Receptores de Interleucina-1/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Yersinia pestis/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA