Ambidextrous helical nanotubes from self-assembly of designed helical hairpin motifs

Academic Article


  • Tandem repeat proteins exhibit native designability and represent potentially useful scaffolds for the construction of synthetic bio-mimetic assemblies. We have designed 2 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 nanotubes. Cryo-electron microscopy with direct electron detection was employed to analyze the structures of the solvated filaments. The 3D reconstructions from the cryo-EM maps led to atomic models for the HEAT_R1 and LRV_M3Δ1 filaments at resolutions of 6.0 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 2 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. Moreover, the resultant nanotubes have independently addressable and chemically distinguishable interior and exterior surfaces that would facilitate applications in selective recognition, transport, and release.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Hughes SA; Wang F; Wang S; Kreutzberger MAB; Osinski T; Orlova A; Wall JS; Zuo X; Egelman EH; Conticello VP
  • Start Page

  • 14456
  • End Page

  • 14464
  • Volume

  • 116
  • Issue

  • 29