JOURNAL ARTICLE

Induction of beta-sheet structure in amyloidogenic peptides by neutralization of aspartate: a model for amyloid nucleation

J Orpiszewski, M D Benson
Journal of Molecular Biology 1999 June 4, 289 (2): 413-28
10366514
Amyloid fibril formation is widely accepted as a critical step in all types of amyloidosis. Amyloid fibrils derived from different amyloidogenic proteins share structural elements including beta-sheet secondary structure and similar tertiary structure. While some amyloidogenic proteins are rich in beta-sheet in their soluble form, others, like Alzheimer beta-amyloid peptide (Abeta) or serum amyloid A, must undergo significant structural transition to acquire a high beta-sheet content. We postulate that Abeta and other amyloidogenic proteins undergo a transition to beta-sheet as a result of aging-related chemical modifications of aspartyl residues to the form of succinimide or isoaspartyl methyl ester. We hypothesize that spontaneous cyclization of aspartate residues in amyloidogenic proteins can serve as a nucleation event in amyloidogenesis. To test this hypothesis, we synthesized a series of designed peptides having the sequence VTVKVXAVKVTV, where X represents aspartic acid or its derivatives. Studies using circular dichroism showed that neutralization of the aspartate residue through the formation of a methyl ester or an amide, or replacement of aspartate with glutamate led to an increased beta-sheet content at neutral and basic pH. A higher content of beta-sheet structure correlated with increased propensity for fibril formation and decreased solubility at neutral pH.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
10366514
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"