Research

April 2005

April 13, 2005

Overview of amyloid assembly mechanisms

Posted by David Talaga

Overview of amyloid Assembly mechanisms

Amyloid – any fibril, plaque, seed, or aggregate that has the characteristic cross-ß sheet structure.
Amyloidogenic precursor – a protein or peptide that upon incubation under appropriate conditions will form amyloid fibrils or plaques.
Amyloid fibril – long ribbons of amyloid ~10nm in diameter and >100nm in length. Most often observed in vitro.
Amyloid plaque – the form of amyloid most often found in vivo – often comprised of aggregated amyloid fibrils.
Amyloid protofibril/filament – a species of amyloid smaller in diameter (3-6nm) and length(<100nm) than typical for amyloid fibrils, thought to be a possible direct precursor to amyloid fibrils perhaps through lateral aggregation.
Amyloid seed (or template) – a species of a critical size or structure that rapidly elongates to form larger amyloid species possibly by providing a proper scaffold for amyloid assembly
Amyloidogenic oligomer – A small aggregate of precursor that is smaller than the critical “seed” size but still may have some of the structural characteristics of amyloid.
Amyloidogenic fold – a structure of the precursor that must be accessed prior to amyloidogenic aggregation, thought to retain substantial secondary structure possibly including some of the native fold. It could be related to a misfolded or molten globule structure.
Folded state – The native (functional) state of the precursor.
Folding intermediate – A partially folded or misfolded structure of the precursor. These partially folded structures are potentially the same as or precursors to amyloidogenic folds.
Denatured state – The unfolded state of the precursor.
Unstructured aggregate – Completely or partially denatured proteins tend to aggregate non-specifically without forming a particular structural motif