α-helical peptide Self-assembly Structure Design and Characterization Público

Abstract

Functionalized nanomaterials are extensively researched in the past decades due to their high functionalization density, and unique physical and mechanical properties compared to their macro-scale material counterparts. Among them, protein and peptide-based nanomaterials are especially sought after, as they encode life-related functions that are often not accessible by current technologies. However, precise control and rational design of protein and peptide-based nanomaterials are difficult to achieve. This thesis presents the design and characterization of three α-helical peptide systems with the recently discovered, novel cross-α tertiary structure that self-assemble into nanofibrils, nanosheets from fibril lamination, and nanotubes from nanosheet wrapping; and the design and characterization of one α-helical coiled-coil peptide system with designed coiled-coil interfaces promoting 2D lateral association of coiled-coil bundles that self-assemble into nanosheets. The results will enhance our understandings of protein self-assembly principles and hopefully contribute to protein and peptide-based nanomaterial designs in the future.

Table of Contents

1..... Chapter 1: Introduction to 1D and 2D Self-assembled Peptide Nanomaterials 23

1.1       Introduction. 23

1.2       α-helix peptide self-assembly. 25

1.3       1D peptide self-assembly based on other structural motifs. 31

1.4       2D peptide self-assembly based on other structural motifs 37

1.5       Conclusion. 40

2..... Chapter 2: PSMα3 Selectively Self-assembles into cross-α Nanotubes 47

2.1       Introduction. 47

2.2       Results and discussion. 53

2.2.1        Self-assembly of PSMα3. 53

2.2.2        Characterization of PSMα3 nanotubes at pH 2. 58

2.2.3        Characterization of PSMα3 nanotubes at pH 8. 68

2.2.4        Screening of amphipathic peptides potentially posing cross-α structures 78

2.3       Conclusion. 81

2.4       Methods 83

3..... Chapter 3: PSMβ2 Self-assembles into cross-α Nanotubes 91

3.1       Introduction. 91

3.2       Results and discussion. 93

3.2.1        Self-assembly of PSMβ1. 93

3.2.2        Self-assembly of PSMβ2. 97

3.2.3        Structural Characterization of the PSMβ2 Nanotubes 101

3.2.4        Structural characterization of other PSMβ2 morphologies 115

3.3       Conclusion. 123

3.4       Methods 124

4..... Chapter 4: Designed Peptide Mimicking Cross-α Amyloid-like Fibrils 129

4.1       Introduction. 129

4.2       Results and discussion. 132

4.2.1        A designed cross cross-α fibril peptide ROX321. 132

4.2.2        Length variants of ROX321. 150

4.2.3        Stacking interface mutants of ROX321. 155

4.3       Conclusion. 161

4.4       Methods 163

5      Chapter 5: Designed 2D Assemblies via Engineering Inter-coiled-coil Bundle Interfaces 174

5.1       Introduction. 174

5.2       Results and discussion. 176

5.2.1        Designs of CC3V2, CC3V7 and CC3V8. 176

5.2.2        Self-assembly of CC3V2, CC3V7 and CC3V8. 181

5.3       Conclusion. 190

5.4       Methods 191

6..... Chapter 6: Conclusion. 200

About this Dissertation

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School	Laney Graduate School
Department	Chemistry
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Chemistry, Biochemistry
Palabra Clave	peptide self-assembly
Committee Chair / Thesis Advisor	Vincent Conticello, Emory University
Committee Members	Khalid Salaita, Emory University David Lynn, Emory University

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