Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Solid-state NMR reveals differences in the packing arrangements of peptide aggregates derived from the aortic amyloid polypeptide medin
AU - Davies, Hannah A
AU - Madine, Jillian
AU - Middleton, David A
N1 - Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.
PY - 2012/1
Y1 - 2012/1
N2 - Several polypeptides aggregate into insoluble amyloid fibrils associated with pathologies such as Alzheimer's disease, Parkinson's disease and type 2 diabetes. Understanding the structural and sequential motifs that drive fibrillisation may assist in the discovery and refinement of effective therapies. Here we investigate the effects of three predicted amyloidogenic regions on the structure of aggregates formed by medin, a poorly characterised polypeptide associated with aortic medial amyloidosis. Solid-state NMR is used to compare the dynamics and sheet packing arrangement of the C-terminal region encompassing residues F(43) GSV within full-length medin (Med(1-50) ) and two shorter peptide fragments, Med(30-50) and Med(42-49) , lacking specific sequences predicted to be amyloidogenic.(.) Results show that all three peptides have different aggregate morphologies, and Med(30-50) and Med(1-50) have different sheet packing arrangements and dynamics to Med(42-49) . These results imply that at least two of the three predicted amyloidogenic regions are required for the formation and elongation of medin fibres observed in the disease state.
AB - Several polypeptides aggregate into insoluble amyloid fibrils associated with pathologies such as Alzheimer's disease, Parkinson's disease and type 2 diabetes. Understanding the structural and sequential motifs that drive fibrillisation may assist in the discovery and refinement of effective therapies. Here we investigate the effects of three predicted amyloidogenic regions on the structure of aggregates formed by medin, a poorly characterised polypeptide associated with aortic medial amyloidosis. Solid-state NMR is used to compare the dynamics and sheet packing arrangement of the C-terminal region encompassing residues F(43) GSV within full-length medin (Med(1-50) ) and two shorter peptide fragments, Med(30-50) and Med(42-49) , lacking specific sequences predicted to be amyloidogenic.(.) Results show that all three peptides have different aggregate morphologies, and Med(30-50) and Med(1-50) have different sheet packing arrangements and dynamics to Med(42-49) . These results imply that at least two of the three predicted amyloidogenic regions are required for the formation and elongation of medin fibres observed in the disease state.
KW - Amino Acid Sequence
KW - Amyloid
KW - Amyloidosis
KW - Antigens, Surface
KW - Aorta
KW - Biological Markers
KW - Diabetes Mellitus, Type 2
KW - Humans
KW - Magnetic Resonance Spectroscopy
KW - Microscopy, Electron
KW - Milk Proteins
KW - Molecular Sequence Data
KW - Neurodegenerative Diseases
KW - Peptide Fragments
KW - Protein Structure, Secondary
KW - Protein Structure, Tertiary
KW - Spectrometry, Fluorescence
KW - Thiazoles
U2 - 10.1002/psc.1418
DO - 10.1002/psc.1418
M3 - Journal article
C2 - 22102261
VL - 18
SP - 65
EP - 72
JO - June 2002. ISSN 1460-4582
JF - June 2002. ISSN 1460-4582
SN - 0893-3200
IS - 1
ER -