Structural determination of a 670 million year old iron-binding protein

6.7 亿年前的铁结合蛋白的结构测定

• 批准号: RGPIN-2017-04894
• 负责人: Jefferies, Wilfred
• 金额: $ 1.89万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629952
• 关键词: Structural; determination; 670; million; year

Iron is a requisite component of most life forms on Earth. The molecule melanotransferrin (MTf) is a member of the transferrin (Tf) family of molecules. It is the most ancient member of the Tf family, dating back over 670 million years. In many species, it exists in both secreted and membrane-anchored forms and has been shown to play a role in transporting iron. Serum Tf carries iron throughout the circulatory system but the unique function(s) and characteristics of MTf in iron transport remain less defined. The 3D structure of MTf has never been determined, and while it is useful to draw comparisons with available crystal structure data for Tf, it is clear that MTf does not bind to the same receptors as Tf. We have evidence that MTf is taken up by a caveolae-dependent pathway rather than the Tf-receptor, clathrin-coated pit mechanism. By comparing the structure of MTf to Tf, we may identify the unique aspects of this ancient iron-binding protein and gain a better understanding of this alternate pathway for iron uptake.s

铁是地球上大多数生命形式的必要组成部分。黑色素转铁蛋白（MTf）分子是转铁蛋白（Tf）分子家族的一员。它是Tf家族中最古老的成员，可以追溯到6.7亿年前。在许多物种中，它以分泌和膜锚定两种形式存在，并已被证明在铁运输中起作用。血清Tf在整个循环系统中携带铁，但MTf在铁运输中的独特功能和特征仍然不太明确。MTf的三维结构从未被确定，虽然与现有的Tf晶体结构数据进行比较是有用的，但很明显，MTf与Tf结合的受体不同。我们有证据表明，MTf是由一个依赖于小泡的途径而不是tf受体，网格蛋白包覆的坑机制。通过比较MTf和Tf的结构，我们可以识别出这种古老的铁结合蛋白的独特之处，并更好地理解这种铁摄取的替代途径