ZiCo:  A Peptide Designed to Switch Folded State upon Binding Zinc

• Published in: Journal of the American Chemical Society Vol. 127; no. 43; pp. 15008 - 15009
• Main Authors: Cerasoli, Eleonora, Sharpe, Belinda K, Woolfson, Derek N
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 02.11.2005
• Subjects: Binding Sites; Biological and medical sciences; Chlorides - chemistry; Chlorides - metabolism; Circular Dichroism; Conformational dynamics in molecular biology; Edetic Acid - chemistry; Edetic Acid - metabolism; Fundamental and applied biological sciences. Psychology; Molecular biophysics; Peptides - chemistry; Peptides - metabolism; Protein Folding; Protein Structure, Secondary; Spectroscopy, Fourier Transform Infrared; Temperature; Zinc - chemistry; Zinc - metabolism; Zinc Compounds - chemistry; Zinc Compounds - metabolism; Amphipathic compound; Helix coil transition; Peptides; Zinc finger structure; Conformational dynamics; Circular dichroism spectrometry; Molecular interaction; NMR spectrometry; Conformational changes; Conformational transition
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0543604

We describe a novel approach to the design of a metal-triggered conformational switch. Specifically, two distinct protein-folding motifs were merged into one polypeptide sequence. The target structures were an α-helical coiled-coil trimer and zinc-bound monomer. Solution-phase spectroscopic, sedimentation, and binding studies confirmed the key aspects of the design. Both forms of the peptide were cooperatively folded, and the switch between them was reversible. This design process potentially presents a novel route to peptide-based biosensors.