Idioma:

A Highly Amyloidogenic Region of Hen Lysozyme

Frare, Erica ; Polverino de Laureto, Patrizia ; Zurdo, Jesús ; Dobson, Christopher M ; Fontana, Angelo

Journal of molecular biology, 2004-07, Vol.340 (5), p.1153-1165 [Periódico revisado por pares]

England: Elsevier Ltd

Texto completo disponível

Citações Citado por

Enviar para

Título:
A Highly Amyloidogenic Region of Hen Lysozyme
Autor: Frare, Erica ; Polverino de Laureto, Patrizia ; Zurdo, Jesús ; Dobson, Christopher M ; Fontana, Angelo
Assuntos: Amino Acid Sequence ; Amyloid - chemistry ; Amyloid - genetics ; Amyloid - metabolism ; Amyloid - ultrastructure ; amyloid fibrils ; Animals ; Chickens ; Chromatography, High Pressure Liquid ; Circular Dichroism ; Cysteine - metabolism ; Disulfides - metabolism ; Hydrogen-Ion Concentration ; limited proteolysis ; lysozyme ; Microscopy, Electron ; Models, Molecular ; Molecular Sequence Data ; Muramidase - chemistry ; Muramidase - genetics ; Muramidase - metabolism ; Muramidase - ultrastructure ; Pepsin A - metabolism ; Peptide Fragments - chemistry ; Peptide Fragments - metabolism ; Protein Denaturation ; protein domains ; Protein Folding ; protein fragments ; Protein Structure, Tertiary ; Temperature
É parte de: Journal of molecular biology, 2004-07, Vol.340 (5), p.1153-1165
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Amyloid fibrils obtained after incubating hen egg-white lysozyme (HEWL) at pH 2.0 and 65 °C for extended periods of time have been found to consist predominantly of fragments of the protein corresponding to residues 49–100, 49–101, 53–100 and 53–101, derived largely from the partial acid hydrolysis of Asp-X peptide bonds. These internal fragments of HEWL encompass part of the β-domain and all the residues forming the C-helix in the native protein, and contain two internal disulfide bridges Cys64–Cys80 and Cys76–Cys94. The complementary protein fragments, including helices A, B and D of the native protein, are not significantly incorporated into the network of fibrils, but remain largely soluble, in agreement with their predicted lower propensities to aggregate. Further analysis of the properties of different regions of HEWL to form amyloid fibrils was carried out by studying fragments produced by limited proteolysis of the protein by pepsin. Here, we show that only fragment 57–107, but not fragment 1–38/108–129, is able to generate well-defined amyloid fibrils under the conditions used. This finding is of particular importance, as the β-domain and C-helix of the highly homologous human lysozyme have been shown to unfold locally in the amyloidogenic variant D67H, which is associated with the familial cases of systemic amyloidosis linked to lysozyme deposition. The identification of the highly amyloidogenic character of this region of the polypeptide chain provides strong support for the involvement of partially unfolded species in the initiation of the aggregation events that lead to amyloid deposition in clinical disease.
Editor: England: Elsevier Ltd
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

A Highly Amyloidogenic Region of Hen Lysozyme

Frare, Erica ; Polverino de Laureto, Patrizia ; Zurdo, Jesús ; Dobson, Christopher M ; Fontana, Angelo

England: Elsevier Ltd

Buscando em bases de dados remotas. Favor aguardar.