Control of Calcium Oxalate Crystal Growth by Face-Specific Adsorption of an Osteopontin Phosphopeptide

详细信息    查看全文

• 作者：Bernd Grohe ; Jason O'Young ; D. Andrei Ionescu ; Gilles Lajoie ; Kem A. Rogers ; Mikko Karttunen ; Harvey A. Goldberg ; Graeme K. Hunter
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：December 5, 2007
• 年：2007
• 卷：129
• 期：48
• 页码：14946 - 14951
• 全文大小：402K
• 年卷期：v.129,no.48(December 5, 2007)
• ISSN：1520-5126

文摘

Mineral-associated proteins have been proposed to regulate many aspects of biomineralization,including the location, type, orientation, shape, and texture of crystals. To understand how proteins achievethis exquisite level of control, we are studying the interaction between the phosphoprotein osteopontin(OPN) and the biomineral calcium oxalate monohydrate (COM). In the present study, we have synthesizedpeptides corresponding to amino acids 220-235 of rat bone OPN (pSHEpSTEQSDAIDpSAEK), one ofseveral highly phosphorylated, aspartic-, and glutamic acid-rich sequences found in the protein. Toinvestigate the role of phosphorylation in interaction with crystals, peptides containing no (P0), one (P1),or all three (P3) phosphates were prepared. Using a novel combination of confocal microscopy and scanningelectron microscopy, we show that these peptides adsorb preferentially to {100} faces of COM and inhibitgrowth of these faces in a phosphorylation-dependent manner. To characterize the mechanism of adsorptionof OPN peptides to COM, we have performed the first atomic-scale molecular-dynamics simulation of aprotein-crystal interaction. P3 adsorbs to the {100} face much more rapidly than P1, which in turn adsorbsmore rapidly than P0. In all cases, aspartic and glutamic acid, not phosphoserine, are the amino acids inclosest contact with the crystal surface. These studies have identified a COM face-specific adsorption motifin OPN and delineated separate roles for carboxylate and phosphate groups in inhibition of crystal growthby mineral-associated phosphoproteins. We propose that the formation of close-range, stable, and face-specific interactions is a key factor in the ability of phosphoproteins to regulate biomineralization processes.