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Title: Ambidextrous Helical Nanotubes from Self-Assembly of Designed Helical Motifs

Abstract

Tandem repeat proteins exhibit native designability and represent potentially useful scaffolds for the construction of synthetic biomimetic assemblies. We have designed two synthetic peptides, HEAT R1 and LRV M3Δ1, based on the consensus sequences of single repeats of thermophilic HEAT (PBS HEAT) and Leucine- Rich Variant (LRV) structural motifs, respectively. Self-assembly of the peptides afforded high aspect-ratio helical helical nanotubes. Cryo-electron microscopy with direct electron detection was employed to analyze the structures of the solvated filaments. Three dimensional reconstructions from the cryo-EM maps led to atomic models for the HEAT R1 and LRV M3Δ1 filaments at resolutions of 6.0 Å and 4.4 Å, respectively. Surprisingly, despite sequence similarity at the lateral packing interface, HEAT R1 and LRV M3Δ1 filaments adopt the opposite helical hand and differ significantly in helical geometry, while retaining a local conformation similar to previously characterized repeat proteins of the same class. The differences in the two filaments could be rationalized on the basis of differences in cohesive interactions at the lateral and axial interfaces. These structural data reinforce previous observations regarding the structural plasticity of helical protein assemblies and the need for high resolution structural analysis. Despite these observations, the native designability of tandem repeat proteinsmore » offers the opportunity to engineer novel helical nanotubes. Furthermore, the resultant nanotubes have independently addressable and chemically distinguishable interior and exterior surfaces that would facilitate applications in selective recognition, transport, and release.« less

Authors:
 [1];  [2];  [3];  [1];  [3];  [3];  [3];  [4];  [3];  [1]
  1. Emory Univ., Atlanta, GA (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)
  3. Univ. of Virginia, Charlottesville, VA (United States)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1525381
Report Number(s):
BNL-211762-2019-JAAM
Journal ID: ISSN 0027--8424
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences; Journal ID: ISSN 0027--8424
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Tandem Repeat Proteins; Cryo-EM; Helical Nanotube; Self-Assembly

Citation Formats

Hughes, Spencer, Wall, Joseph, Wang, Fengbin, Wang, Shengyuan, Kreutzberger, Mark, Osinski, Tomasz, Orlova, Albina, Zuo, Xiaobing, Egelman, Edward, and Conticello, Vincent. Ambidextrous Helical Nanotubes from Self-Assembly of Designed Helical Motifs. United States: N. p., 2019. Web. doi:10.1073/pnas.1903910116.
Hughes, Spencer, Wall, Joseph, Wang, Fengbin, Wang, Shengyuan, Kreutzberger, Mark, Osinski, Tomasz, Orlova, Albina, Zuo, Xiaobing, Egelman, Edward, & Conticello, Vincent. Ambidextrous Helical Nanotubes from Self-Assembly of Designed Helical Motifs. United States. doi:10.1073/pnas.1903910116.
Hughes, Spencer, Wall, Joseph, Wang, Fengbin, Wang, Shengyuan, Kreutzberger, Mark, Osinski, Tomasz, Orlova, Albina, Zuo, Xiaobing, Egelman, Edward, and Conticello, Vincent. Wed . "Ambidextrous Helical Nanotubes from Self-Assembly of Designed Helical Motifs". United States. doi:10.1073/pnas.1903910116.
@article{osti_1525381,
title = {Ambidextrous Helical Nanotubes from Self-Assembly of Designed Helical Motifs},
author = {Hughes, Spencer and Wall, Joseph and Wang, Fengbin and Wang, Shengyuan and Kreutzberger, Mark and Osinski, Tomasz and Orlova, Albina and Zuo, Xiaobing and Egelman, Edward and Conticello, Vincent},
abstractNote = {Tandem repeat proteins exhibit native designability and represent potentially useful scaffolds for the construction of synthetic biomimetic assemblies. We have designed two synthetic peptides, HEAT R1 and LRV M3Δ1, based on the consensus sequences of single repeats of thermophilic HEAT (PBS HEAT) and Leucine- Rich Variant (LRV) structural motifs, respectively. Self-assembly of the peptides afforded high aspect-ratio helical helical nanotubes. Cryo-electron microscopy with direct electron detection was employed to analyze the structures of the solvated filaments. Three dimensional reconstructions from the cryo-EM maps led to atomic models for the HEAT R1 and LRV M3Δ1 filaments at resolutions of 6.0 Å and 4.4 Å, respectively. Surprisingly, despite sequence similarity at the lateral packing interface, HEAT R1 and LRV M3Δ1 filaments adopt the opposite helical hand and differ significantly in helical geometry, while retaining a local conformation similar to previously characterized repeat proteins of the same class. The differences in the two filaments could be rationalized on the basis of differences in cohesive interactions at the lateral and axial interfaces. These structural data reinforce previous observations regarding the structural plasticity of helical protein assemblies and the need for high resolution structural analysis. Despite these observations, the native designability of tandem repeat proteins offers the opportunity to engineer novel helical nanotubes. Furthermore, the resultant nanotubes have independently addressable and chemically distinguishable interior and exterior surfaces that would facilitate applications in selective recognition, transport, and release.},
doi = {10.1073/pnas.1903910116},
journal = {Proceedings of the National Academy of Sciences},
number = ,
volume = ,
place = {United States},
year = {2019},
month = {5}
}

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This content will become publicly available on May 29, 2020
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