Acylation of Lens Proteins
晶状体蛋白的酰化
基本信息
- 批准号:9765327
- 负责人:
- 金额:$ 39.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:Acetyl Coenzyme AAcetylationAcyl Coenzyme AAcylationAdoptedAdvanced Glycosylation End ProductsAgeAgingAmino AcidsBiochemicalBiochemical ReactionBlindnessCataractCellsChemicalsCrystallinsCysteineDataExhibitsHumanIn VitroLeadLipidsLysineMalonyl Coenzyme AMeasuresMediatingModificationMolecular ChaperonesMutationN acylationOxidesPathway interactionsPatternPost-Translational Protein ProcessingPresbyopiaProteinsReactionSirtuinsSiteSolubilityStructureTestingTissuesTransferaseTranslatingVisual impairmentacyl groupage effectage relatedagedalpha-Crystallinsamino groupbasecase-basedchemical reactionexperimental studyglycationimprovedlenslens transparencynovel therapeuticspreventpropionyl-coenzyme Aprotein crosslinkprotein structure functionresiliencesuccinyl-coenzyme Atherapy developmentwater solubility
项目摘要
N-acylation of cytosolic proteins is a common occurrence in tissues, and it regulates protein structure and
function. The major N-acylation types in cells are acetylation, propionylation, succinylation and malonylation,
which are initiated by the enzymatic or non-enzymatic transfer of acetyl CoA, propionyl CoA, succinyl CoA
and malonyl CoA to lysine residues, respectively. Lens proteins are long lived with little or no turnover, and
thus, post-translational modifications (PTMs) accumulate with age. The lack of enzymatically active proteins,
particularly in the core of the lens, prohibits the reversal of PTMs. Thus, if deacylases are weak in the lens,
acylation is mostly a one-way reaction that leads to permanent modifications of lens proteins, which appears
to be the case (based on our preliminary data). The effects of acylation on lens proteins remain largely
unknown. As shown in our previous study, the acetylation makes α-crystallin a better chaperone. In addition,
our preliminary data show that lens proteins are also propionylated, succinylated and malonylated and that
acetylation and succinylation increase the thermal stability and solubility of the proteins. Thus, we
hypothesize that acylation of lens proteins is a beneficial PTM that helps maintain the chaperone activity of α-
crystallin as well as the stability and solubility of lens proteins during aging. We will test this hypothesis in
three aims. In Aim 1, we will determine the major acylation sites in human lens α-crystallin by mass
spectrometric analyses and determine the effect of age on these modifications. In Aim 2, we will determine
effects of acylation on the structure and function of α-crystallin. In Aim 3, we will evaluate the effects of
acylation on the stability and solubility of lens proteins and determine whether acylation can be used to
improve the compromised resilience of aged human lenses.
胞质蛋白的n -酰化在组织中很常见,它调节着蛋白质的结构和功能
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ram H Nagaraj其他文献
Ram H Nagaraj的其他文献
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{{ truncateString('Ram H Nagaraj', 18)}}的其他基金
Molecular mechanisms of protein crosslinking in the lens
晶状体中蛋白质交联的分子机制
- 批准号:
8999881 - 财政年份:2015
- 资助金额:
$ 39.33万 - 项目类别:
Molecular mechanisms of protein crosslinking in the lens
晶状体中蛋白质交联的分子机制
- 批准号:
8887124 - 财政年份:2015
- 资助金额:
$ 39.33万 - 项目类别:
Molecular mechanisms of protein crosslinking in the lens
晶状体中蛋白质交联的分子机制
- 批准号:
9117569 - 财政年份:2015
- 资助金额:
$ 39.33万 - 项目类别:
Molecular Mechanisms of Protein Crosslinking in the Lens
晶状体中蛋白质交联的分子机制
- 批准号:
8482333 - 财政年份:2013
- 资助金额:
$ 39.33万 - 项目类别:
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