5VTE

Hetero antiparallel coiled coil hexamer formed by de novo peptides

Summary for 5VTE

• Entry DOI: 10.2210/pdb5vte/pdb
• Descriptor: de novo peptide 1, de novo peptide 2 (3 entities in total)
• Functional Keywords: antiparallel, hexamer, de novo, phe-ile zipper, de novo protein
• Biological source: synthetic construct; More
• Total number of polymer chains: 2
• Total formula weight: 6877.65

Authors

Spencer, R.K.,Hochbaum, A.I. (deposition date: 2017-05-16, release date: 2017-10-04, Last modification date: 2022-12-14)

Primary citation

Spencer, R.K.,Hochbaum, A.I.
The Phe-Ile Zipper: A Specific Interaction Motif Drives Antiparallel Coiled-Coil Hexamer Formation.
Biochemistry, 56:5300-5308, 2017

PubMed Abstract: Coiled coils are a robust motif for exploring amino acid interactions, generating unique supramolecular structures, and expanding the functional properties of biological materials. A recently discovered antiparallel coiled-coil hexamer (ACC-Hex, peptide 1) exhibits a unique interaction in which Phe and Ile residues from adjacent α-helices interact to form a Phe-Ile zipper within the hydrophobic core. Analysis of the X-ray crystallographic structure of ACC-Hex suggests that the stability of the six-helix bundle relies on specific interactions between the Phe and Ile residues. The Phe-Ile zipper is unprecedented and represents a powerful tool for utilizing the Phe-Ile interactions to direct supramolecular assembly. To further probe and understand the limits of the Phe-Ile zipper, we designed peptide sequences with natural and unnatural amino acids placed at the Phe and Ile residue positions. Using size exclusion chromatography and small-angle X-ray scattering, we found that the proper assembly of ACC-Hex from monomers is sensitive to subtle changes in side chain steric bulk and hydrophobicity introduced by mutations at the Phe and Ile residue positions. Of the sequence variants that formed ACC-Hex, mutations in the hydrophobic core significantly affected the stability of the hexamer, from a ΔG of 2-8 kcal mol. Additional sequences were designed to further probe and enhance the stability of the ACC-Hex system by maximizing salt bridging between the solvent-exposed residues. Finally, we expanded on the generality of the Phe-Ile zipper, creating a unique sequence that forms an antiparallel hexamer that is topologically similar to ACC-Hex but atomistically unique.

PubMed: 28876052
DOI: 10.1021/acs.biochem.7b00756

Experimental method

X-RAY DIFFRACTION (2.023 Å)