We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Structural insights into peptide self‐assembly using photo‐induced crosslinking experiments and discontinuous molecular dynamics.
- Authors
Bunce, Samuel J.; Wang, Yiming; Radford, Sheena E.; Wilson, Andrew J.; Hall, Carol K.
- Abstract
Determining the structure of the (oligomeric) intermediates that form during the self‐assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo‐induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid‐forming peptide, Aβ16‐22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*16–22). Electrospray ionization ion‐mobility spectrometry mass‐spectrometry (ESI‐IMS‐MS) analysis of the PIC products confirmed that Aβ*16–22 forms assemblies with the monomers arranged as anti‐parallel, in‐register β‐strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ16‐22 assembles through a single‐step nucleation into a β‐sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ16‐22 self‐assembly processes, paving the way to explore the self‐assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.
- Subjects
MOLECULAR dynamics; FLUORESCENCE quenching; PEPTIDE amphiphiles; MOLECULAR structure; AMINO acids; MONOMERS
- Publication
AIChE Journal, 2021, Vol 67, Issue 3, p1
- ISSN
0001-1541
- Publication type
Article
- DOI
10.1002/aic.17101