Structural Plasticity of Helical Nanotubes Based on Coiled-Coil Assemblies

Abstract

Numerous instances can be seen in evolution where protein quaternary structures have diverged while the sequences of the building blocks have remained fairly conserved. However, the path through which such divergence has taken place is usually not known. We have designed two synthetic 29-residue α-helical peptides, based on the coiled-coil structural motif, that spontaneously self-assemble into helical nanotubes in vitro. Using electron cryo-microscopy (cryo-EM) with a newly available direct electron detection capability, we can achieve near-atomic resolution of these thin structures. We show how conservative changes of only one or two amino acids results in dramatic changes in quaternary structure, in which the assemblies can be switched between two very different forms. This system provides a framework for understanding how small sequence changes in evolution can translate into very large changes in supramolecular structure, a phenomenon that may have significant implications for the de novo design of synthetic peptide assemblies.

The Glycolytic Enzyme Phosphofructokinase-1 Assembles into Filaments

“…The asymmetry in assembly interfaces between the A and B dimers of PFKL was unusual among helical filaments with multimeric helical asymmetric units. Typically, each protomer makes identical assembly contacts, although asymmetries like the one seen in this study have been seen previously (Egelman et al, 2015).…”

Self-Assembly of Open Protein Systems: A Comprehensive View Based onthe Interactions between 3d Hydrophobic and Electric Dipole MomentVectors

“…H/D index goes from 4.25 of monomers to almost 9.0 in the assembly. e. Helical Nanotubes PDBid: 3J89, [25]. In this case the basic element for growth is a tetramer arranged as a closed assembly by itself.…”

Structure-Function Analysis of the ϕX174 DNA-Piloting Protein Using Length-Altering Mutations

“…Furthermore, it shares sequence similarities with T7 DNA-piloting proteins that form tail tube extensions during infection (2, 8). Thus, H protein serves as a paradigm for the assembly and function of long ␣-helical supramolecular structures and nanotubes (12,13).Protein H likely assumes multiple conformations during the X174 life cycle. For DNA translocation, 10 proteins form a 170-Å-long ␣-helical tube that is separated into two domains.…”

“…Furthermore, it shares sequence similarities with T7 DNA-piloting proteins that form tail tube extensions during infection (2, 8). Thus, H protein serves as a paradigm for the assembly and function of long ␣-helical supramolecular structures and nanotubes (12,13).…”