Identification of cross-linking pattern in human elastin

人类弹性蛋白交联模式的鉴定

• 批准号: 188218494
• 负责人: Dr. Andrea Heinz
• 金额: --
• 依托单位: Department of Pharmacy
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/188218494?language=en
• 关键词: Identification; cross; linking; pattern; human

Elastin is an essential protein of the extracellular matrix of vertebrates and possesses unique properties such as elasticity, resilience and extreme durability, which make it crucial for the long-term function of different tissues and organs such as aorta, lung, skin or cartilage. The biopolymer is composed of units of its precursor tropoelastin, which are connected via lysine residues and form a variety of polyfunctional cross-links. Due to its high hydrophobicity and complex cross-linking pattern elastin is completely insoluble and very resistant to enzymatic degradation, which limits structure investigations. Hence, virtually nothing is known about the cross-linking pattern of elastin in different human tissues. It is, however, of major importance to investigate the structure of elastin on the molecular level to better understand its functions in healthy tissues as well as structural changes that go along with cardiovascular diseases such as atherosclerosis, lung emphysema and aortic stenosis. Moreover, detailed insights into the structure of elastic fibers will aid in the development of protein-based biomaterials, which may be used for a variety of medical applications. Therefore, the aim of this project is the development and the application of analytical and bioinformatics methods to characterize the cross-linking pattern of elastin isolated from human aorta. Based on different model systems such as cross-linked elastin peptides, cross-linked elastin polypeptides and cross-linked tropoelastin mass spectrometric methods will be developed, which enable identifying and sequencing cross-links characteristic of elastin. Controlled degradation of isolated elastin using specific elastases and subsequent identification of cross-linked peptides will then allow to determine the exact positions of inter- and intramolecular cross-links as well as the domains of tropoelastin molecules involved in cross-linking. The project will provide a comprehensive and significant insight into the structure of elastin. Overall, understanding the structure of elastin will support the development of directed therapies against diseases of elastic tissues, including enzyme inhibitors, wound regeneration materials or vascular prostheses.

弹性蛋白是脊椎动物细胞外基质的必需蛋白质，具有弹性、弹性和极端耐久性等独特特性，这对于主动脉、肺、皮肤或软骨等不同组织和器官的长期功能至关重要。该生物聚合物由其前体弹性蛋白原单元组成，这些单元通过赖氨酸残基连接并形成各种多官能交联。由于其高疏水性和复杂的交联模式，弹性蛋白完全不溶并且对酶降解具有很强的抵抗力，这限制了结构研究。因此，实际上对不同人体组织中弹性蛋白的交联模式一无所知。然而，在分子水平上研究弹性蛋白的结构非常重要，以便更好地了解其在健康组织中的功能以及与动脉粥样硬化、肺气肿和主动脉瓣狭窄等心血管疾病相关的结构变化。此外，对弹性纤维结构的详细了解将有助于开发基于蛋白质的生物材料，该材料可用于各种医疗应用。因此，该项目的目的是开发和应用分析和生物信息学方法来表征从人主动脉分离的弹性蛋白的交联模式。基于不同的模型系统，如交联弹性蛋白肽、交联弹性蛋白多肽和交联原弹性蛋白质谱方法，将开发出能够识别和测序弹性蛋白交联特征的方法。使用特定的弹性蛋白酶对分离的弹性蛋白进行受控降解以及随后对交联肽的鉴定将允许确定分子间和分子内交联的确切位置以及参与交联的原弹性蛋白分子的结构域。该项目将为弹性蛋白的结构提供全面而重要的见解。总体而言，了解弹性蛋白的结构将支持开发针对弹性组织疾病的定向疗法，包括酶抑制剂、伤口再生材料或血管假体。

项目成果

Fingerprinting Desmosine-Containing Elastin Peptides

• DOI: 10.1007/s13361-014-1075-9
• 发表时间: 2015-05-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Schraeder, Christoph U.;Heinz, Andrea;Schmelzer, Christian E. H.
• 通讯作者: Schmelzer, Christian E. H.

In vitro cross-linking of elastin peptides and molecular characterization of the resultant biomaterials.

弹性蛋白肽的体外交联以及所得生物材料的分子表征

• DOI: 10.1016/j.bbagen.2013.01.014
• 发表时间: 2013
• 期刊: Biochimica et biophysica acta
• 作者: A. Heinz;C.K.H. Ruttkies;G. Jahreis;C.U. Schräder;K. Wichapong;W. Sippl;F.W. Keeley;R.H.H. Neubert;C.E.H. Schmelzer
• 通讯作者: C.E.H. Schmelzer

Elastins from patients with Williams–Beuren syndrome and healthy individuals differ on the molecular level

WilliamsâBeuren 综合征患者和健康个体的弹性蛋白在分子水平上存在差异

• DOI: 10.1002/ajmg.a.37638
• 发表时间: 2016
• 期刊: American Journal of Medical Genetics Part A
• 影响因子: 2
• 作者: A. Heinz;A.C. Mora Huertas;C.U. Schräder;R. Pankau;A. Gosch;C.E.H. Schmelzer
• 通讯作者: C.E.H. Schmelzer

Does human leukocyte elastase degrade intact skin elastin?

• DOI: 10.1111/febs.12012
• 发表时间: 2012-11-01
• 期刊: FEBS JOURNAL
• 影响因子: 5.4
• 作者: Schmelzer, Christian E. H.;Jung, Michael C.;Heinz, Andrea
• 通讯作者: Heinz, Andrea