title: Molecular recognition at the protein-hydroxyapatite interface.
abstract: Proteins found in mineralized tissues act as nature's crystal engineers, where they play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (bones/teeth) and calcium oxalate (kidney stones). Despite their importance in hard-tissue formation and remodeling, and in pathological processes such as stone formation and arterial calcification, there is little known of the protein structure-function relationships that govern hard-tissue engineering. Here we review early studies that have utilized solid-state NMR (ssNMR) techniques to provide in situ secondary-structure determination of statherin and statherin peptides on their biologically relevant hydroxyapatite (HAP) surfaces. In addition to direct structural study, molecular dynamics studies have provided considerable insight into the protein-binding footprint on hydroxyapatite. The molecular insight provided by these studies has also led to the design of biomimetic fusion peptides that utilize nature's crystal-recognition mechanism to display accessible and dynamic bioactive sequences from the HAP surface. These peptides selectively engage adhesion receptors and direct specific outside-in signaling pathway activation in osteoblast-like cells.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. stayton@u.washington.edu
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Stayton
authors.forename: Gary P
authors.initials: GP
authors.lastname: Drobny
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Shaw
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Long
authors.forename: Michele
authors.initials: M
authors.lastname: Gilbert
mesh_terms: D003460:Crystallization; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins; D012471:Salivary Proteins and Peptides / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011993:Recombinant Fusion Proteins; C018149:STATH protein, human; D012471:Salivary Proteins and Peptides; D017886:Durapatite