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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [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)
+ Show Author Affiliations

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.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
SC0012704; AC02-06CH11357
OSTI ID:
1525381
Alternate ID(s):
OSTI ID: 1563920
Report Number(s):
BNL-211762-2019-JAAM
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 29; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 28 works
Citation information provided by
Web of Science

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Figures / Tables (6)

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Fig. 3(p. 5)figure Fig. 3
Table 1(p. 5)table Table 1
Fig. 4(p. 6)figure Fig. 4
Fig. 5(p. 6)figure Fig. 5

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59 BASIC BIOLOGICAL SCIENCES
Tandem Repeat Proteins
Cryo-EM
Helical Nanotube
Self-Assembly
cryo-EM
helical nanotube
self-assembly
tandem repeat proteins