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Nano Research

Article Title

Site-specific determination of TTR-related functional peptides by using scanning tunneling microscopy

Authors

Lanlan Yu, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China Department of Chemistry, Tsinghua University, Beijing 100084, China University of Chinese Academy of Sciences, Beijing 100049, China
Yongfang Zheng, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China Department of Chemistry, Tsinghua University, Beijing 100084, China University of Chinese Academy of Sciences, Beijing 100049, China
Jing Xu, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Fuyang Qu, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Yuchen Lin, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Yimin Zou, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China University of Chinese Academy of Sciences, Beijing 100049, China
Yanlian Yang, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China
Sally L. Gras, Department of Chemical and Biomolecular Engineering and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia
Chen Wang, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, CAS Center for Excellence in Brain Science, National Center for Nanoscience and Technology, Beijing 100190, China

Keywords

TTR1, functional peptide, key site, scanning tunneling microscopy (STM), optimization

Abstract

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.

Graphical Abstract

Publisher

Tsinghua University Press

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