Peptide plane flipping

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Peptide plane flipping is a type of conformational change that can occur in proteins by which the dihedral angles of adjacent amino acids undergo large-scale rotations with little displacement of the side chains. The plane flip is defined as a rotation of the dihedral angles φ,ψ at amino acids i and i+1 such that the resulting angles remain in structurally stable regions of Ramachandran space. The key requirement is that the sum of the ψi angle of residue i and the φi+1 angle of residue i+1 remain roughly constant; in effect, the flip is a crankshaft move about the axis defined by the Cα-Cˡ and N-Cα bond vectors of the peptide group, which are roughly parallel. As an example, the type I and type II beta turns differ by a simple flip of the central peptide group of the turn.

Peptide plane flips have been observed in the dynamics of native state protein tertiary structures by comparing crystal structures of the same proteins in multiple conformations. However, the most important role of plane flipping is thought to be in the process of early protein folding rather than native-state local fluctuations.[1]

Peptide plane flipping provides a relatively low-energy pathway from alpha sheet or left-handed alpha helix to beta strand conformations. This has been suggested as a mechanism in the conformational changes of amyloid beta and related amyloidogenic peptides implicated in protein misfolding diseases such as Alzheimer's disease. These peptides may pass through an alpha-sheet intermediate in forming the beta-sheet-rich amyloid fiber assembly.[2][3]

References

  1. Hayward S. (2001). Peptide-plane flipping in proteins. Protein Sci 10(11):2219-27. PMID 11604529
  2. Daggett V. (2006). Alpha-sheet: The toxic conformer in amyloid diseases? Acc Chem Res 39(9):594-602. PMID 16981675
  3. Armen RS, DeMarco ML, Alonso DO, Daggett V. (2004). Pauling and Corey's alpha-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease. Proc Natl Acad Sci USA 101(32):11622-7. PMID 15280548

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