Selective Protein−Protein Interactions Driven by a Phenylalanine Interface

• Published in: Journal of the American Chemical Society Vol. 128; no. 1; pp. 188 - 191
• Main Authors: Yoder, Nicholas C, Kumar, Krishna
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 11.01.2006
• Subjects: Amino Acid Sequence; Biological and medical sciences; Circular Dichroism; Fundamental and applied biological sciences. Psychology; Interactions. Associations; Intermolecular phenomena; Molecular biophysics; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Phenylalanine - chemistry; Phenylalanine - metabolism; Protein Conformation; Substrate Specificity; Thermodynamics; Binding capacity; Phenylalanine; Molecular assembly; Chemical affinity; Circular dichroism spectrometry; Hydrophobic interaction; Molecular interaction; Protein; Aminoacid sequence
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja055494k

Highly specific protein−protein interfaces have been the subject of considerable study for their potential utility in disrupting or interrogating cellular signaling and control networks. We report that coiled-coil sequences decorated with phenylalanine core residues fold into stable α-helical bundles and that these self-sort from similar peptide assemblies with aliphatic core side chains. For self-assembled ensembles derived from 30-residue monomeric peptides, the ΔG of specificity is −1.5 kcal/mol, comparable with earlier self-sorting coiled-coil systems. Intriguingly, although this interface is constructed from canonical amino acids, it does not appear to have been exploited in native proteins.