Site-specific determination of TTR-related functional peptides by using scanning tunneling microscopy
TTR1, functional peptide, key site, scanning tunneling microscopy (STM), optimization
ABSTRACT For the design and optimization of functional peptides, unravelling the structures of individual building blocks as well as the properties of the ensemble is paramount. TTR1, derived from human transthyretin, is a fibril-forming peptide implicated in diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The functional peptide TTR1-RGD, based on a TTR1 scaffold, was designed to specifically interact with cells. Here, we used scanning tunneling microscopy (STM) to analyze the assembly structures of TTR1-related peptides with both the reverse sequence and the modified forward sequence. The sitespecific analyses show the following: i) The TTR1 peptide is involved in assembly, nearly covering the entire length within the ordered -sheet structures. ii) For TTR1-RGD peptide assemblies, the TTR1 motif forms the ordered β-sheet while the RGDS motif adopts a flexible conformation allowing it to promote cell adhesion. The key site is clearly identified as the linker residue Gly13. iii) Close inspection of the forward and reverse peptide assemblies show that in spite of the difference in chemistry, they display similar assembling characteristics, illustrating the robust nature of these peptides. iv) Glycine linker residues are included in the -strands, which strongly suggests that the sequence could be optimized by adding more linker residues. These garnered insights into the assembled structures of these peptides help unravel the mechanism driving peptide assemblies and instruct the rational design and optimization of sequenceprogrammed peptide architectures.
Tsinghua University Press
Lanlan Yu,Yongfang Zheng,Jing Xu,Fuyang Qu,Yuchen Lin,Yimin Zou,Yanlian Yang,Sally L. Gras,Chen Wang, Site-specific determination of TTR-related functional peptides by using scanning tunneling microscopy. NanoRes.2018, 11(1): 577–585