Structure/function studies of a cyclomodulin

环调节蛋白的结构/功能研究

• 批准号: BB/F008732/1
• 负责人: Mark Banfield
• 金额: $ 53.96万
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF008732%2F1
• 关键词: Structure; function; studies; cyclomodulin

Proteins are a biological molecules encoded by a gene, and they are the molecular machines of life. Proteins form a complex 3-dimensional structure that frequently determines their function. A protein's function is usually dependent on interaction with another molecule and this interaction leads to an effect. The experiments described in this proposal aim to investigate the structure and function of a protein from pathogenic bacteria that is able to change the properties of the host cell during infection. Specifically this protein, called 'Cif' interferes with progression of the host cell cycle (process of growth and division), irreversibly stopping it in its tracks. Although it is not currently understood why, this presumably has some benefit for the invading bacteria. Studying proteins such as this is important for both understanding host-pathogen interactions (the molecular causes of disease) and the host cell processes themselves. For instance, a deregulated cell cycle is often linked to development of cancer, and proteins that regulate the cell cycle are one of the most targeted set of molecules by the pharmaceutical industry. How Cif actually brings about its effect in host cells is not currently understood. One powerful approach to determining how this protein functions is to look at its structure. This can be visualised using a technique called X-ray crystallography followed by reconstruction of a model using computer graphics. Once the structure is known alterations to the protein can be designed to further investigate protein function in host cells. Also important for understanding Cif function is identifying the protein's molecular targets within host cells (most likely other proteins), characterising the interaction (how strongly do they bind to each other?), and ultimately determining the structure of molecules together. This would generate a picture of a bacterial protein interacting with a host cell protein, and a complex responsible for transducing an effect ultimately leading to host cell cycle arrest. Understanding the nature of these interactions for Cif has long-term applications for development of novel therapeutics targeting host-pathogen interactions and also carcinogenesis.

蛋白质是一种由基因编码的生物分子，是生命的分子机器。蛋白质形成复杂的三维结构，经常决定它们的功能。蛋白质的功能通常依赖于与另一个分子的相互作用，这种相互作用会导致某种效果。本实验旨在研究病原菌中一种在感染过程中能够改变宿主细胞特性的蛋白的结构和功能。具体来说，这种被称为“Cif”的蛋白质会干扰宿主细胞周期的进程（生长和分裂的过程），不可逆转地阻止宿主细胞周期的进程。虽然目前还不清楚原因，但这可能对入侵细菌有一些好处。研究这样的蛋白质对于理解宿主-病原体相互作用（疾病的分子原因）和宿主细胞本身的过程都很重要。例如，细胞周期失控通常与癌症的发展有关，而调节细胞周期的蛋白质是制药行业最具针对性的一组分子之一。Cif如何在宿主细胞中发挥作用目前尚不清楚。确定这种蛋白质如何起作用的一个有效方法是观察它的结构。这可以用一种叫做x射线晶体学的技术来可视化，然后用计算机图形学重建一个模型。一旦结构已知，就可以设计改变蛋白质，进一步研究蛋白质在宿主细胞中的功能。对理解Cif功能同样重要的是识别宿主细胞内蛋白质的分子靶标（很可能是其他蛋白质），表征相互作用（它们彼此结合的强度如何？），并最终确定分子的结构。这将生成细菌蛋白与宿主细胞蛋白相互作用的图像，以及负责转导最终导致宿主细胞周期阻滞的效应的复合体。了解Cif的这些相互作用的性质对开发针对宿主-病原体相互作用和致癌作用的新疗法具有长期的应用价值。

项目成果

Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.

• DOI: 10.1371/journal.pone.0005582
• 发表时间: 2009
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Crow A;Race PR;Jubelin G;Varela Chavez C;Escoubas JM;Oswald E;Banfield MJ
• 通讯作者: Banfield MJ

Cycle inhibiting factors (CIFs) are a growing family of functional cyclomodulins present in invertebrate and mammal bacterial pathogens.

• DOI: 10.1371/journal.pone.0004855
• 发表时间: 2009
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Jubelin G;Chavez CV;Taieb F;Banfield MJ;Samba-Louaka A;Nobe R;Nougayrède JP;Zumbihl R;Givaudan A;Escoubas JM;Oswald E
• 通讯作者: Oswald E

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction.

丁香假单胞菌 III 型效应子 HopAF1 通过靶向蛋氨酸回收来阻止乙烯诱导，从而抑制植物免疫。

• DOI: 10.1073/pnas.1606322113
• 发表时间: 2016
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Washington EJ

Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

丁香假单胞菌 III 型效应子 HopAF1 通过靶向蛋氨酸回收来阻止乙烯诱导来抑制植物免疫

• DOI: 10.17615/401c-wa73
• 发表时间: 2016
• 作者: Banfield, Mark J.