Polymorphism in peptide self-assembly visualized

Abstract

The spontaneous formation of well-defined supramolecular structures, based on precisely located, finely balanced, and weak, relative to kT, interactions among the assembling subunits, is a useful definition of self-assembly. The recognition that proteins could spontaneously refold from their denatured states (1), demonstrating that the information required to assemble the tertiary structure of a protein is built into the primary structure, was an early indicator of the biological importance and power of self-assembly processes. Spontaneous thermodynamically means moving down a free energy gradient seeking a global minimum, but, of course, it does not mean instantaneous dynamically. Self-assembly processes have pathways, kinetics, and other intricacies of moving over and sampling complex free energy landscapes, and do not always land in the global free energy minimum, demonstrated, for example, by the pathologies related to protein misfolding (2). Organization of native and unnatural proteins and peptides into micelles, sheets, tubules, fibers, filaments, and other multimolecular structures by self-assembly, subject to similar influences as folding of individual protein molecules, also happens in nature and via synthetic molecular engineering. The supramolecular assembly of peptides, often with engineered hydrophobicity, chirality, or other modifications, has proven useful in making materials (3), vaccines (4), and therapeutics, exemplified in the PNAS paper by Pieri et al. (5), in which the structure of the assembly formed from the synthetic octapeptide Lanreotide has been determined at high resolution by cryotransmission electron microscopy (cryo-TEM). Lanreotide is similar to a natural chemical called somatostatin, which is produced in the body by the hypothalamus and functions inter alia to modulate the secretion of growth … [↵][1] 1Email: mtirrell{at}uchicago.edu. [1]: #xref-corresp-1-1