Structural thermodynamics of complex carbohydat recognition by proteins

蛋白质识别复杂碳水化合物的结构热力学

• 批准号: 153396481
• 负责人: Professorin Dr. Stefanie Barbirz
• 金额: --
• 依托单位: Institut für Biochemie und Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/153396481?language=en
• 关键词: Structural; thermodynamics; complex; carbohydat; recognition

The specific binding of complex oligosaccharides by proteins is at the heart of numerous biological recognition processes. It is central to physiological cell-cell interactions, as well as tumor formation in animals, the establishment of symbiotic interactions between plants and bacteria, and many infection processes throughout all kingdoms of biology. Structural and biophysical data on such recognition processes are scarce, as the interaction partners often are not accessible in biochemical quantities. We have isolated several bacteriophage tailspike proteins recognizing complex oligosaccharide structures on the cell surfaces of the bacterial host cells of the phages and determined high-resolution crystal structures of the corresponding protein-carbohydrate complexes. Biochemical amounts of the binding partners are easily accessible in high purity from natural sources. Moreover, the proteins have high thermostability. This makes these systems exceptionally well suited for structural thermodynamics studies. To investigate the driving forces in the formation of protein complexes with complex oligosaccharides, we will undertake a thorough thermodynamic characterization of the binding interactions between tailspike proteins and oligosaccharides using a combination of biochemical and biophysical methods. Mutant proteins and oligosaccharides of different length and composition will be employed to identify sources of specificity. Our data will help understanding and predicting biological recognition processes and will be highly relevant for molecular medicine and biotechnology.

蛋白质对复杂寡糖的特异性结合是许多生物识别过程的核心。它是生理细胞间相互作用、动物肿瘤形成、植物和细菌之间共生相互作用的建立以及整个生物学领域的许多感染过程的核心。这种识别过程的结构和生物物理数据是稀缺的，因为相互作用的伙伴往往无法获得生化量。我们已经分离出几种噬菌体尾刺蛋白，识别噬菌体细菌宿主细胞表面的复杂寡糖结构，并确定了相应的蛋白质-碳水化合物复合物的高分辨率晶体结构。生物化学量的结合伙伴很容易获得高纯度的天然来源。此外，蛋白质具有较高的热稳定性。这使得这些系统非常适合于结构热力学研究。为了研究蛋白质与寡糖复合物形成的驱动力，我们将利用生物化学和生物物理方法的结合，对尾穗蛋白与寡糖之间的结合相互作用进行彻底的热力学表征。突变蛋白和不同长度和组成的寡糖将被用来确定特异性的来源。我们的数据将有助于理解和预测生物识别过程，并将与分子医学和生物技术高度相关。

项目成果

Tail morphology controls DNA release in two Salmonella phages with one lipopolysaccharide receptor recognition system

• DOI: 10.1111/j.1365-2958.2012.08006.x
• 发表时间: 2012-03-01
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Andres, Dorothee;Roske, Yvette;Barbirz, Stefanie
• 通讯作者: Barbirz, Stefanie

In Vitro Studies of Lipopolysaccharide-Mediated DNA Release of Podovirus HK620

• DOI: 10.3390/v10060289
• 发表时间: 2018-06-01
• 期刊: VIRUSES-BASEL
• 影响因子: 4.7
• 作者: Broeker, Nina K.;Kiele, Franziska;Barbirz, Stefanie
• 通讯作者: Barbirz, Stefanie

Solvent Networks Tune Thermodynamics of Oligosaccharide Complex Formation in an Extended Protein Binding Site.

• DOI: 10.1021/jacs.8b03719
• 发表时间: 2018-07
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Sonja Kunstmann;U. Gohlke;N. Broeker;Y. Roske;U. Heinemann;M. Santer;S. Barbirz

Bacteriophage tailspike protein based assay to monitor phase variable glucosylations in Salmonella O-antigens

基于噬菌体尾刺蛋白的测定法监测沙门氏菌 O 抗原中的相变糖基化

• DOI: 10.1186/s12866-016-0826-0
• 发表时间: 2016
• 期刊: BMC Microbiology
• 影响因子: 4.2
• 作者: Schmidt;Rabsch;Broeker;Barbirz
• 通讯作者: Barbirz