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Proteomic Approaches to Protein Fatty Acylation

蛋白质脂肪酰化的蛋白质组学方法

基本信息

批准号：
7910658
负责人：
Julian P Whitelegge
金额：
$ 28.59万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7910658
关键词：
Address Alzheimer&apos s Disease Biochemistry Biology Biophysics Cell physiology Characteristics Chromatography Code Collection Complement Complex Mixtures Data Detection Development Digestion Dimensions Disease Dissociation Electrons Genotype Goals Human Human Genome Ions Lipids Liquid substance Malignant Neoplasms Mass Spectrum Analysis Measures Membrane Modification Nature Neurodegenerative Disorders Peptides Phase Physical Chemistry Pilot Projects Plasma Plasma Proteins Play Population Post-Translational Protein Processing Property Protein Analysis Protein Chemistry Protein Fragment Proteins Proteolysis Proteome Proteomics Protocols documentation Recovery Relative (related person)Resolution Role Shotguns Site Solubility Technology Time Variant aqueous chemical cleavage experience fatty acylation improved innovation mass spectrometer nano novel protein folding protein protein interaction public health relevance research study reversed phase chromatography tandem mass spectrometry two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Proteomic approaches to protein fatty acylation Protein lipidation is a fundamentally important cellular process that functions in protein folding, protein targeting, membrane interaction and protein/protein interactions. It plays significant roles in cancer and neurodegenerative disease though our understanding of the exact nature of these roles is relatively poor. Discovery of new protein lipidation targets will potentially impact other diseases. Unfortunately, shotgun proteomics workflows that simplify proteins to a collection of peptides tend not to detect lipidated peptides, probably because the protocols employed are optimized to the most easily recovered soluble peptides (proteotypic). Addressing the bias against protein lipidation detection in proteomics requires novel innovations in separations technologies for bottom-up approaches and specialized top-down or middle-down approaches when targeting intact lipidated proteins. Specific aim one will focus on efficient digestion of lipidated proteins and subsequent recovery of lipidated peptides via enrichment with novel HILIC chromatography protocols. We will also innovate modified reverse-phase protocols for recovery of long- chain acylated peptides and tandem mass spectrometry. The overall goal will be a robust two-dimensional separation technology for proteome-wide detection and characterization of lipidated peptides. Specific aim two will focus development of top-down mass spectrometry technologies for characterization of lipidated proteins. This aim includes MSMSMS strategies as well as middle-down strategies to target robust localization of lipidation sites. The overall goal will be a robust mass spectrometry /protein chemistry technology for top-down analysis of protein lipidation across the proteome. PUBLIC HEALTH RELEVANCE: The diversity of proteins coded in the human genome perform the majority of cellular functions that allow human beings to thrive. Some proteins are modified to make them greasy (fatty acylation or lipidation) thereby modulating their function desirably, or in diseases including some cancers and possibly Alzheimer's Disease undesirably. We propose to develop new proteomics technologies to accurately describe and measure this important protein modification that has to date been poorly detected.

描述（由申请人提供）：蛋白质脂肪酰化的蛋白质组学方法蛋白质脂化是一个基本重要的细胞过程，在蛋白质折叠，蛋白质靶向，膜相互作用和蛋白质/蛋白质相互作用中起作用。它在癌症和神经退行性疾病中发挥着重要作用，尽管我们对这些作用的确切性质的了解相对较少。新的蛋白脂化靶点的发现将潜在地影响其他疾病。不幸的是，将蛋白质简化为肽集合的散弹枪蛋白质组学工作流程往往无法检测到脂化肽，这可能是因为所采用的方案是针对最容易回收的可溶性肽（蛋白质型）进行优化的。解决蛋白质组学中对蛋白质脂化检测的偏见需要在针对完整脂化蛋白的自下而上方法和专门的自上而下或中向下方法的分离技术方面进行创新。具体目标之一将集中在脂化蛋白的有效消化和随后的回收脂化肽通过富集与新的HILIC色谱协议。我们还将创新改进的反相方案，用于长链酰化肽的恢复和串联质谱分析。总体目标将是一个强大的二维分离技术，用于蛋白质组范围的检测和表征脂化肽。具体目标二将重点发展自上而下的质谱技术，用于表征脂化蛋白。这一目标包括MSMSMS策略以及针对脂化位点的稳健定位的中下策略。总体目标将是一种强大的质谱/蛋白质化学技术，用于自上而下分析蛋白质组中的蛋白质脂化。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mass spectrometric measurements of the apolipoproteins of bovine (Bos taurus) HDL.

牛 (Bos taurus) HDL 载脂蛋白的质谱测量。

DOI：
10.1016/j.cbd.2011.10.001
发表时间：
2012
期刊：
Comparative biochemistry and physiology. Part D, Genomics & proteomics
影响因子：
0
作者：
DellaDonna,Lorenza;Bassilian,Sara;Souda,Puneet;Nebbia,Carlo;Whitelegge,JulianP;Puppione,DonaldL
通讯作者：
Puppione,DonaldL

Proteogenomic Review of the Changes in Primate apoC-I during Evolution.

灵长类 apoC-I 进化过程中变化的蛋白质组学综述。

DOI：
10.1007/s11515-013-1278-7
发表时间：
2013
期刊：
Frontiers in biology
影响因子：
0
作者：
Puppione,Donald;Whitelegge,JulianP
通讯作者：
Whitelegge,JulianP

Mass spectral measurements of the apoHDL in horse (Equus caballus) cerebrospinal fluid.

马 (Equus caballus) 脑脊液中 apoHDL 的质谱测量。

DOI：
10.1016/j.cbd.2012.02.002
发表时间：
2012
期刊：
Comparative biochemistry and physiology. Part D, Genomics & proteomics
影响因子：
0
作者：
Puppione,DonaldL;DellaDonna,Lorenza;Bassilian,Sara;Souda,Puneet;MacDonald,MelindaH;Whitelegge,JulianP
通讯作者：
Whitelegge,JulianP

Structural biology. Up close with membrane lipid-protein complexes.

结构生物学。