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Polymers and Self Assembly: From Biology to Nanomaterials
Tuesday Speaker Abstracts
Solid-State NMR Structural Characterization of Peptide Assemblies: Oligomeric Aβ(1-42)
and Designer Peptide Nanofibers
Anant K. Paravastu
.
Georgia Institute of Technology, Atlanta, USA.
Our group has focused on probing structures of self-assembled peptides using solid-state NMR
spectroscopy. For the 42-residue Alzheimer’s amyloid-β peptide (Aβ(1-42)), emerging
understanding of environment-dependent assembly pathways has made it possible to produce
oligomeric samples with a stable homogeneous molecular structure. We seek to understand how
oligomeric structures are distinct from fibrillar structures in order to provide a structural basis for
differing neuronal toxicity profiles. We are also interested in designer peptides with amino acid
sequences that were rationally designed to promote specific self-assembled molecular structures.
We will show how the combination of solid-state NMR and constrained molecular dynamics
computer simulations could provide the specific structural information necessary to test proposed
structural models from the literature. For 150 kDa Aβ(1-42) oligomers, we will show data in
support of an antiparallel β-sheet structure that is distinct from the in-register parallel motif
commonly observed for amyloid fibrils. We will present a structural model for RADA16-I
designer nanofibers that is composed of parallel β-sheets, unlike the antiparallel β-sheet structure
proposed in the literature. For the MAX8 designer peptide, we will present direct evidence of
proposed β-hairpin formation. For the SAF-p1/p2 system, we will show inter-molecular side
chain contacts that are consistent with an α-helical coiled-coil nanofiber structure. We will use
these results to evaluate our overall ability to predict and control self-assembled peptide
molecular structures.