Parallel β‑Sheet Structure and Structural Heterogeneity Detected within Q11 Self-Assembling Peptide Nanofibers
Q11 peptide nanofibers are used as a biomaterial for applications such as antigen presentation and tissue engineering, yet detailed knowledge of molecular-level structure has not been reported. The Q11 peptide sequence was designed using heuristics-based patterning of hydrophobic and polar amino aci...
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Published in | The journal of physical chemistry. B Vol. 128; no. 22; pp. 5387 - 5396 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
06.06.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Q11 peptide nanofibers are used as a biomaterial for applications such as antigen presentation and tissue engineering, yet detailed knowledge of molecular-level structure has not been reported. The Q11 peptide sequence was designed using heuristics-based patterning of hydrophobic and polar amino acids with oppositely charged amino acids placed at opposite ends of the sequence to promote antiparallel β-sheet formation. In this work, we employed solid-state nuclear magnetic resonance spectroscopy (NMR) to evaluate whether the molecular organization within Q11 self-assembled peptide nanofibers is consistent with the expectations of the peptide designers. We discovered that Q11 forms a distribution of molecular structures. NMR data from two-dimensional (2D) 13C–13C dipolar-assisted rotational resonance indicate that the K3 and E9 residues between Q11 β-strands are spatially proximate (within ∼0.6 nm). Frequency-selective rotational echo double resonance (fsREDOR) on K3 Nζ and E9 Cδ-labeled sites showed that approximately 9% of the sites are close enough for salt bridge formation to occur. Surprisingly, dipolar recoupling measurements revealed that Q11 peptides do not assemble into antiparallel β-sheets as expected, and structural analysis using Fourier-transform infrared spectroscopy and 2D NMR alone can be misleading. 13C PITHIRDS-CT dipolar recoupling measurements showed that the most abundant structure consists of parallel β-sheets, in contrast to the expected antiparallel β-sheet structure. Structural heterogeneity was detected from 15N{13C} REDOR measurements, with approximately 22% of β-strands having antiparallel nearest neighbors. We cannot propose a complete structural model of Q11 nanofibers because of the complexity involved when examining structurally heterogeneous samples using NMR. Altogether, our results show that while heuristics-based patterning is effective in promoting β-sheet formation, designing a peptide sequence to form a targeted β-strand arrangement remains challenging. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1520-6106 1520-5207 1520-5207 |
DOI: | 10.1021/acs.jpcb.4c00825 |