CAREER: Metal Transport by the Primitive Monolobal Transferrin

该职业奖由无机、生物无机和有机金属化学项目颁发，支持耶鲁大学Ann M. Valentine教授对单粒转铁蛋白携带金属特性的研究。在脊椎动物和其他高等生物中，铁（III）通过转铁蛋白在血清中携带。这些转铁蛋白是两叶蛋白，其中每个蛋白质分子的前后半叶或叶彼此高度相似，每个叶都有一个金属原子的结合位点。最近在一种海洋无脊椎动物，海鞘或海鞘中发现了一种前体单瓣形式。这种单球蛋白的可用性使人们能够研究在氧化环境中携带金属的能力是如何进化的，特别是转铁蛋白是否曾经是一种被优化为最紧密结合铁的普通金属载体。目的：从海鞘中分离和表征单粒转铁蛋白，测定其与金属的结合紧密度，建立其与金属的结合机制，确定金属释放的机制和条件。这个项目研究了一种古老形式的蛋白质，这种蛋白质在血液中运输铁。这项研究的目的是了解这种蛋白质的进化，以及它是如何对铁有更强的选择性的。研究将与教育活动相结合，其特点是为非专业学生开设一门以生物无机化学为平台的基础化学入门课程，以及一个指导和科学推广计划。

This CAREER award by the Inorganic, Bioinorganic, and Organometallic Chemistry Program supports work by Professor Ann M. Valentine at Yale University to study the metal-carrying properties of the monolobal transferrin protein. In vertebrates and other higher organisms, iron(III) is carried in the serum by transferrin. These transferrins are two-lobed proteins, in which the front and back halves or lobes of each protein molecule are highly similar to one another, and each lobe has a binding site for one metal atom. A precursor monolobal form was recently discovered in a marine invertebrate, the ascidian or sea squirt. The availability of this monolobal protein enables investigations into how the capacity evolved to carry metals in an oxidizing environment, and specifically whether transferrin was once a general metal carrier that was optimized to bind iron most tightly. The objectives are to isolate and characterize the monolobal transferrin from the ascidian Ciona intestinalis, to measure the tightness and establish the mechanism of metal binding, and to determine the mechanisms and conditions for metal release. This project investigates an ancient form of the protein which transports iron in the blood. The research is directed toward understanding the evolution of this protein and how it became more selective for iron. Research will be integrated with educational activities, featuring the development of an introductory course for non-majors that uses bioinorganic chemistry as a platform on which to teach fundamental chemistry, and a program of mentoring and scientific outreach.