title: Hydroxyapatite surface-induced peptide folding.
abstract: Herein, we describe the design and surface-binding characterization of a de novo designed peptide, JAK1, which undergoes surface-induced folding at the hydroxyapatite (HA)-solution interface. JAK1 is designed to be unstructured in buffered saline solution, yet undergo HA-induced folding that is largely governed by the periodic positioning of gamma-carboxyglutamic acid (Gla) residues within the primary sequence of the peptide. Circular dichroism (CD) spectroscopy and analytical ultracentrifugation indicate that the peptide remains unfolded and monomeric in solution under normal physiological conditions; however, CD spectroscopy indicates that in the presence of hydroxyapatite, the peptide avidly binds to the mineral surface adopting a helical structure. Adsorption isotherms indicate nearly quantitative surface coverage and Kd = 310 nM for the peptide-surface binding event. X-ray photoelectron spectroscopy (XPS) coupled with the adsorption isotherm data suggests that JAK1 binds to HA, forming a self-limiting monolayer. This study demonstrates the feasibility of using HA surfaces to trigger the intramolecular folding of designed peptides and represents the initial stages of defining the design rules that allow HA-induced peptide folding.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Capriotti
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Beebe
authors.forename: Joel P
authors.initials: JP
authors.lastname: Schneider
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium; D017886:Durapatite / Q000737:chemistry*; D053613:Janus Kinase 1 / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012995:Solubility; D013499:Surface Properties
chemical_list: D010455:Peptides; D017886:Durapatite; D053613:Janus Kinase 1; D002118:Calcium