amyloid deposit
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Definition: Any fibril, plaque, seed, or aggregate that has the characteristic cross-ß sheet structure.
Amyloid deposits derived from diverse precursors share many structural features.
Amyloid fibrils share a common core filament structure, irrespective of the nature of their precursor proteins.
X-ray and electron diffraction studies of amyloid fibrils have confirmed the generality of the cross-ß helical structure present in amyloid with ß-Strands separated by 4.7Å and ß-sheets separated by 9.8Å.
The ß-sheet structure has the strands perpendicular to the long axis of the fibril and hydrogen bonded along the axis of the fibril.
Filaments typically have two or more ß-sheets that are stacked normal to the helical axis and extend along it. Fibrils are composed of two or more filaments.
Histological staining of various amyloid deposits exhibits a common behavior. Congo red shows green birefringence and thioflavin T (ThT) shows a new profluorescent absorption band that that are both thought to be related to the common cross-ß core structure.
Linear birefringence and dichroism of Congo red has been used to determine the relative orientation of fibrils within amyloid plaques in situ.
This type of non-covalent labeling is sensitive to the presence of the quaternary interactions specific to fully-formed amyloid.
NMR has also been used to determine the residue-level participation in the core structure of amyloid fibrils using H/D exchange and relaxation measurements.
These results show that the segments of ß-stands that comprise the core of the fibrils is are protected from access to water and are more rigidly held than the loops or ends that are not part of the core.
Conformational changes
Conformational changes are typically observed during amyloid assembly.
In their native state, the precursor proteins may not, in general, contain the secondary structural elements present in the final amyloid assembly.
The amide I infrared absorption or Raman band is typically observed to lose intensity associated with the native state and gain intensity associated with cross-ß.
Circular dichroism of the peptide backbone absorption band is also sensitive to secondary structure and gives similar results.
Fluorescence spectroscopy can also be used to detect conformational changes either by non-covalent labeling with dyes like ANS that are specific for exposed hydrophobic patches or through covalent attachment of fluorescent dyes.
See also
amyloidoses