Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide

Atomic structure of Lanreotide nanotubes revealed by cryo-EM

“…The resulting complexity of the nanotube structure, with eight peptides in the asymmetric unit, would be impossible to imagine from the interpretation of spectroscopic and low-resolution structural data that existed in 2003. The revolution in high-resolution cryo-EM has had a profound impact in the structural biology of large protein complexes, but is just beginning to impact assemblies of small natural and synthetic peptides ( 11 , 15 – 18 ).…”

“…To enable rational design of peptide material requires a deep understanding of the chemical and physicochemical rules guiding peptide assemblies and folding. However, what can be seen in many peptide assemblies is “deterministic chaos” ( 11 ), where we simply lack the tools at this point to predict how such peptides may assemble and the potentially polymorphic assemblies that may form. Since these assemblies usually result from deterministic chemical interactions, they are all potentially predictable, but we need many more structures to develop the tools needed to make such predictions.…”

“…However, the actual high-resolution cryoelectron microscopy (cryo-EM) structure of the Lanreotide nanotube exhibits different molecular conformations and packing. In addition to showing an unsuspected polymorphism for Lanreotide, the atomic structure of the nanotubes again shows the power of the cryo-EM approach in studying peptide assemblies and the difficulty in predicting the way that small peptides self-assemble, due in part to the multiple conformations a peptide can adopt within assemblies ( 11 ).…”

The emergence of order: A closer look at peptide assembly and its complexity

“…7 Recent achievements in cryogenic electron microscopy (Cryo-EM)recognized with the 2017 Nobel Prize in chemistry to Jacques Dubochet, Joachim Frank, and Richard Hendersonhave shaken the field of structural characterization. 6,8,9 Cryo-EM allows the acquisition of the different folded and even functional states of newly discovered peptides and proteins at atomic resolution, which facilitates mechanistic elucidation and accelerates potential therapeutic development. Cryo-EM structural reconstruction can also help in resolving the conformation of natural and de novo peptide supramolecular structures, which would then provide the critical feedback required to match structural design and assembly assessment.…”

“…Cryo-EM structural reconstruction can also help in resolving the conformation of natural and de novo peptide supramolecular structures, which would then provide the critical feedback required to match structural design and assembly assessment. 8 In the article published by Wang et al, 9 a step forward is taken towards detailed understanding of the self-assembly of an amphiphilic octapeptide monomer (Ac-FKFEFKFE-NH2, KFE8). Surprisingly, KFE8 exhibits a much more complex organization pattern than could be a priori predicted.…”