Journal
PROTEIN SCIENCE
Volume 11, Issue 2, Pages 342-349Publisher
WILEY
DOI: 10.1110/ps.48702
Keywords
amylin; islet amyloid polypeptide; IAPP; amyloid; deamidation; protein aggregation; diabetes mellitus; chemical modification
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Funding
- NIGMS NIH HHS [GM54233, R29 GM054233, R01 GM054233] Funding Source: Medline
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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.
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