NSF-BSF: Novel determinants of prokaryotic copper homeostasis

NSF-BSF：原核铜稳态的新决定因素

• 批准号: 1938715
• 负责人: Amy Rosenzweig
• 金额: $ 79.71万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1938715&HistoricalAwards=false
• 关键词: NSF; BSF; Novel; determinants; prokaryotic

Metals are essential nutrients for all life forms. In particular, copper plays a role in respiration and antioxidant defense. However, too much copper is toxic and can damage cells. Therefore, specific proteins are used to bind copper and carry it to different cellular locations. Since metals are present in one third of all proteins, studying their transport and delivery is of fundamental importance and impacts understanding of many biological and environmental processes, including global element cycles. The goal of this project is to investigate how bacteria obtain and distribute copper. The project will provide opportunities for interdisciplinary research training at all levels as well as for mentoring and outreach in the local community. Moreover, the project will present a unique opportunity for scientists from the US and Israel to work closely together, leading to expanded skillsets and experiences with diverse scientific communities and ways of conducting research. Such exposure is an essential component of training scientists in an increasingly global society.Since prokaryotic copper enzymes are extracytoplasmic, most research has addressed either copper import to the periplasm for enzyme loading or mechanisms of copper resistance, with little focus on the possibility of controlled cytoplasmic copper import. Nevertheless, growing evidence suggests that import to the cytoplasm may be required for loading of some periplasmic copper enzymes. Putative cytoplasmic copper importers include members of the CopD/YcnJ/YebZ family of transmembrane proteins. Genes encoding these proteins are typically found associated with genes encoding periplasmic copper binding proteins, such as CopCs and other yet-to-be characterized proteins. This project will investigate both periplasmic and transmembrane proteins implicated in cyotplasmic copper import, focusing primarily on systems found in E. coli. The approach combines genetic, computational, biophysical, and structural methods that leverage the complementary expertises of the collaborating laboratories in the US and Israel. The research will result in elucidation of the structure and function of previously uncharacterized copper-binding proteins and will lead to new models of bacterial copper homeostasis.This collaborative US/Israel project is supported by the US National Science Foundation and the Israeli Binational Science Foundation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

金属是所有生命形式所必需的营养物质。特别值得一提的是，铜在呼吸和抗氧化防御中发挥着作用。然而，太多的铜是有毒的，可能会损害细胞。因此，特定的蛋白质被用来结合铜并将其携带到不同的细胞位置。由于金属存在于所有蛋白质的三分之一中，因此研究它们的运输和输送对于理解许多生物和环境过程，包括全球元素循环具有重要意义。这个项目的目标是调查细菌是如何获得和分配铜的。该项目将为各级的跨学科研究培训以及在当地社区提供指导和外联提供机会。此外，该项目将为美国和以色列的科学家提供一个密切合作的独特机会，从而扩大与不同科学界的技能和经验，并以不同的方式开展研究。在日益全球化的社会中，这种暴露是培训科学家的重要组成部分。由于原核生物铜酶是胞外的，大多数研究要么讨论了铜进入周质用于酶负载的可能性，要么研究了铜抗性的机制，很少关注控制细胞质铜进口的可能性。然而，越来越多的证据表明，可能需要输入细胞质来装载一些周质铜酶。推测的细胞质铜进口者包括COPD/YcnJ/YebZ跨膜蛋白家族的成员。编码这些蛋白的基因通常与编码周质铜结合蛋白的基因有关，如COPCs和其他尚未确定特征的蛋白。这个项目将研究胞质铜进口中涉及的周质和跨膜蛋白，主要集中在在大肠杆菌中发现的系统。该方法结合了遗传、计算、生物物理和结构方法，利用了美国和以色列合作实验室的互补专业知识。这项研究将有助于阐明以前未知的铜结合蛋白的结构和功能，并将导致细菌铜稳态的新模型。这一美国/以色列合作项目得到了美国国家科学基金会和以色列双国科学基金会的支持。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。