Research Projects

Proteins

Aβ - Structural Details of the Monomer

We examine a range of Aβ peptides of various lengths and with various point mutations and look for specific structural elements such as loops, turns, and short sections of helix initiated by a specific amino acid sequence. A current working hypothesis is that certain structural elements of the monomer nucleate protein folding which in turn facilitates aggregation. Of particular interest are the sequence A²¹EDVGSNKGA³⁰ and the hydrophobic C-terminal tail G²⁹AIIGLMVGGVVIA⁴² which, in the full-length protein Aβ(1-42) and as fragments Aβ(21-30) and Aβ(29-42), are resistant to limited proteolysis. Our structural studies have focused on the peptides

• Aβ(1-42)
• Aβ(21-30)
• C-terminal fragments Aβ(x-42) and Aβ(x-40), x = 29 to 39

with wild-type sequences and sequences with selected point mutations.

• Figure 4. Schematic representation of Aβ42 conformations in the early stages of aggregation. Monomers without helical structure are in equilibrium with monomers containing small amounts of helical structure at the C-terminus. Five or six monomers assemble to form a paranucleus where the hydrophobic C-termini are shielded by the more hydrophilic parts of the peptides. Hydrophobic residues are marked in blue.

See also:

• Our study: Amyloid β-protein monomer structure: A computational and experimental study [3]
• Our study: Structure of the 21-30 fragment of amyloid β-protein [4]
• Our web page: Peptide Folding