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Title: Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides

Abstract

Dentin phosphoprotein (DPP) is the most acidic protein in vertebrates and structurally is classified as an intrinsically disordered protein. Functionally, DPP is related to dentin and bone formation, however the specifics of such association remain unknown. Here, we used atomistic molecular dynamics simulations to screen selected binding domains of DPP onto hydroxyapatite (HA), which is one of its important interacting partners. From these results, we selected a functionally relevant peptide, Ace-SSDSSDSSDSSDSSD-NH2 (named P5) and its phosphorylated form (named P5P), for experimental characterization. SAXS experiments indicated that in solution P5 was disordered, possibly in an extended conformation while P5P displayed more compact globular conformations. Circular dichroism and FTIR confirmed that, either in the presence or absence of Ca2 +/HA, P5 adopts a random coil structure, whereas its phosphorylated counterpart, P5P, has a more compact arrangement associated with conformations that display β-sheet and α-helix motifs when bound to HA. In solution, P5 inhibited HA crystal growth, whereas at similar concentrations, P5P stimulated it. These findings suggest that phosphorylation controls the transient formation of secondary and tertiary structure of DPP peptides, and, most likely of DPP itself, which in turn controls HA growth in solution and possibly HA growth in mineralized tissues.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1409580
Report Number(s):
BNL-114632-2017-JA¿¿¿
Journal ID: ISSN 8756-3282
DOE Contract Number:  
SC0012704
Resource Type:
Journal Article
Resource Relation:
Journal Name: Bone; Journal Volume: 95; Journal Issue: C
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Villarreal-Ramirez, Eduardo, Eliezer, David, Garduño-Juarez, Ramon, Gericke, Arne, Perez-Aguilar, Jose Manuel, and Boskey, Adele. Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides. United States: N. p., 2017. Web. doi:10.1016/j.bone.2016.10.028.
Villarreal-Ramirez, Eduardo, Eliezer, David, Garduño-Juarez, Ramon, Gericke, Arne, Perez-Aguilar, Jose Manuel, & Boskey, Adele. Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides. United States. doi:10.1016/j.bone.2016.10.028.
Villarreal-Ramirez, Eduardo, Eliezer, David, Garduño-Juarez, Ramon, Gericke, Arne, Perez-Aguilar, Jose Manuel, and Boskey, Adele. Wed . "Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides". United States. doi:10.1016/j.bone.2016.10.028.
@article{osti_1409580,
title = {Phosphorylation regulates the secondary structure and function of dentin phosphoprotein peptides},
author = {Villarreal-Ramirez, Eduardo and Eliezer, David and Garduño-Juarez, Ramon and Gericke, Arne and Perez-Aguilar, Jose Manuel and Boskey, Adele},
abstractNote = {Dentin phosphoprotein (DPP) is the most acidic protein in vertebrates and structurally is classified as an intrinsically disordered protein. Functionally, DPP is related to dentin and bone formation, however the specifics of such association remain unknown. Here, we used atomistic molecular dynamics simulations to screen selected binding domains of DPP onto hydroxyapatite (HA), which is one of its important interacting partners. From these results, we selected a functionally relevant peptide, Ace-SSDSSDSSDSSDSSD-NH2 (named P5) and its phosphorylated form (named P5P), for experimental characterization. SAXS experiments indicated that in solution P5 was disordered, possibly in an extended conformation while P5P displayed more compact globular conformations. Circular dichroism and FTIR confirmed that, either in the presence or absence of Ca2 +/HA, P5 adopts a random coil structure, whereas its phosphorylated counterpart, P5P, has a more compact arrangement associated with conformations that display β-sheet and α-helix motifs when bound to HA. In solution, P5 inhibited HA crystal growth, whereas at similar concentrations, P5P stimulated it. These findings suggest that phosphorylation controls the transient formation of secondary and tertiary structure of DPP peptides, and, most likely of DPP itself, which in turn controls HA growth in solution and possibly HA growth in mineralized tissues.},
doi = {10.1016/j.bone.2016.10.028},
journal = {Bone},
number = C,
volume = 95,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}