Low levels of asparagine deamidation can have a dramatic effect on aggregation of amyloidogenic peptides: implications for the study of amyloid formation.
The polypeptide hormone amylin forms amyloid deposits in Type 2 diabetes mellitus and a 10-residue fragment of amylin (amylin(20-29)) is commonly used as a model system to study this process. Studies of amylin(20-29) and several variant peptides revealed that low levels of deamidation can have a significant effect on the secondary structure and aggregation behavior of these molecules. Results obtained with a variant of amylin(20-29), which has the primary sequence SNNFPAILSS, are highlighted. This peptide is particularly interesting from a technical standpoint. In the absence of impurities the peptide does not spontaneously aggregate and is not amyloidogenic. This peptide can spontaneously deamidate, and the presence of less than 5% of deamidation impurities leads to the formation of aggregates that have the hallmarks of amyloid. In addition, small amounts of deamidated material can induce amyloid formation by the purified peptide. These results have fundamental implications for the definition of an amyloidogenic sequence and for the standards of purity of peptides and proteins used for studies of amyloid formation.
Nilsson
Melanie R
MR
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA.
Driscoll
Miles
M
Raleigh
Daniel P
DP
D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D001216:Asparagine / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003224:Congo Red; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared
D000577:Amides; D000682:Amyloid; D010446:Peptide Fragments; D012996:Solutions; D003224:Congo Red; D001216:Asparagine