权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Structural, spatial, and temporal features guiding amelogenins transformation of calcium phosphate into enamel

引导牙釉蛋白将磷酸钙转化为牙釉质的结构、空间和时间特征

基本信息

批准号：
10681277
负责人：
Wendy J Shaw
金额：
$ 48.76万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-19 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10681277
关键词：
3-Dimensional Adsorption Affect Amelogenesis Imperfecta Amino Acid Substitution Amino Acids Atomic Force Microscopy Binding Coupled Crystallization Dental Enamel Development Disease Enamel Formation Extracellular Matrix Goals Growth Hydroxyapatites In Situ In Vitro Individual Ions Knockout Mice Knowledge Maps Microscopic Minerals Modification Molecular Morphology Mus Mutation N-terminal Nanosphere Natural regeneration Nature Needles Outcome Persons Phase Phase Transition Phenotype Process Property Proteins Raman Spectrum Analysis Research Roentgen Rays Role Scanning Site Spatial Distribution Spectrum Analysis Structure System Techniques Therapeutic Time Tissues Variant Vertebrates Work X ray microscopy amelogenin biomineralization calcium phosphate design falls in vivo insight malformation mineralization mouse model nanoscale particle prevent protein distribution protein protein interaction protein structure repaired solid state nuclear magnetic resonance spatial relationship tomography tool transmission process

项目摘要

Project Summary The goal of the proposed work is to develop a molecular level, structural understanding of the role of amelogenin in directing the hierarchical growth of enamel. Enamel is one of the hardest biominerals known, and is hierarchically structured to prevent crack propagation, allowing it to last many people a lifetime. However, naturally occurring diseases or damage do occur to enamel and our current therapies fall far short of nature made enamel. Over the past decade we have come to understand that amelogenin assembles into quaternary structures as oligomers containing 12 proteins, units which further assemble into nanospheres. These assemblies, the molecular level interactions governing them, their interactions with calcium phosphate, and their role in mineral phase transformations, are not well understood for enamel formation. We do know that the protein amelogenin, the predominant protein in the forming enamel milieu, is critical in formation based on amelogenin null mouse models showing severely damaged enamel phenotypes. Protein structure often dictates function, yet we have only begun to reveal the structure of amelogenin. Further, the mineral in the enamel milieu begins as ions, and transitions through an amorphous stage prior to becoming elongated, crystallized HAP needles. Both in vivo and in vitro studies have demonstrated that amelogenin controls this phase transformation process, but the structural, spatial, and temporal aspects of this process are not understood. In our proposed work, we bring a set of advanced characterization techniques to an in vitro system simulating developing enamel to evaluate the structure of amelogenin when interacting with calcium phosphates, to understand the spatial distribution of amelogenin around developing calcium phosphate mineral ribbons, and to develop a molecular level view of the transformation process from calcium phosphate clusters, through the amorphous phase, on to crystalline HAP. This suite of techniques has never been brought to bear on understanding the challenge of enamel growth and will result in an understanding of the development of enamel that is currently lacking. The results of this work are relevant to biomineralization systems in general and may ultimately inform more robust therapeutics for enamel replacements.

项目总结

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A solution NMR investigation into the impaired self-assembly properties of two murine amelogenins containing the point mutations T21→I or P41→T.

DOI：
10.1016/j.abb.2013.07.015
发表时间：
2013-09-15
期刊：
Archives of biochemistry and biophysics
影响因子：
3.9
作者：
Buchko GW;Lin G;Tarasevich BJ;Shaw WJ
通讯作者：
Shaw WJ

Adsorption of amelogenin onto self-assembled and fluoroapatite surfaces.

DOI：
10.1021/jp804548x
发表时间：
2009-02-19
期刊：
The journal of physical chemistry. B
影响因子：
0
作者：
Tarasevich BJ;Lea S;Bernt W;Engelhard M;Shaw WJ
通讯作者：
Shaw WJ

Meeting report: a hard look at the state of enamel research.

会议报告：仔细研究搪瓷研究的状态。

DOI：
10.1038/ijos.2017.40
发表时间：
2017-11-22
期刊：
International journal of oral science
影响因子：
14.9
作者：
Klein OD;Duverger O;Shaw W;Lacruz RS;Joester D;Moradian-Oldak J;Pugach MK;Wright JT;Millar SE;Kulkarni AB;Bartlett JD;Diekwisch TG;DenBesten P;Simmer JP
通讯作者：
Simmer JP

Sequence-Defined Energetic Shifts Control the Disassembly Kinetics and Microstructure of Amelogenin Adsorbed onto Hydroxyapatite (100).