Aggregation of an amyloidogenic fragment of human islet amyloid polypeptide.
Native human islet amyloid polypeptide (hIAPP) has been identified as the major component of amyloid plaques found in the pancreatic islets of Langerhans of persons affected by type 2 diabetes mellitus. Early studies of hIAPP determined that a segment of the molecule, amino acids 20-29, is responsible for its aggregation into amyloid fibrils. The present study demonstrates that the aggregation of hIAPP 20-29-Trp is a nucleation-dependent process, displaying a distinct lag time before the onset of rapid aggregation. Moreover, the lag time can be eliminated by seeding the sample of unaggregated peptide with preformed fibrils. In contrast to the expectation from the conventional model of nucleation-dependent aggregation, however, the lag time of hIAPP aggregation does not depend on peptide concentration. To explain this observation, a modified version of the standard model of nucleation-dependent aggregation is presented in which the monomeric peptide concentration is buffered by an off-aggregation-pathway formation of peptide micelles.
Rhoades
E
E
Institute of Gerontology, University of Michigan, 300 North Ingalls, Box 2007, Ann Arbor, MI 48109, USA.
Agarwal
J
J
Gafni
A
A
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments