MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS

说明：本提案的重点是结构和功能 广泛分布的富含半胱氨酸的金属结合蛋白 金属硫蛋白（MT）。 MT在38年前被发现，但其生理学 角色尚未确认。 然而，其生物合成受到以下因素的密切调控： 暴露于重金属离子，并结合广泛的实验 关于金属结合的数据，导致了一个建议，即MT是一个关键的 金属稳态的组成部分。 这项工作的一个中心重点是 确定三个MT的3D溶液结构，一个哺乳动物，一个来自 粗糙脉孢菌和蓝蟹的一种。 在以往的研究中， 金属离子不稳定性已被证明为3-金属簇在β 域 结果表明，分子间交换发生在 β位点，该提议的另一个目标是阐明 这种金属交换现象的机制和动力学细节。

DESCRIPTION: This proposal has as its focus the structural and functional role of the ubiquitously distributed cysteine-rich metal binding protein metallothionein (MT). MT was discovered 38 years ago, but its physiological role remains unconfirmed. However, its biosynthesis is closely regulated by exposure to heavy metal ions and in combination with extensive experimental data on metal binding, has lead to a proposal that MT is a critical component in metal homeostasis. A central focus of this work will be to determine 3D solution structures of three MTs, one mammalian, one from Neurospora crassa and one from the blue Crab. In previous studies unique metal-ion lability has been demonstrated for the 3-metal cluster in beta domain. It was demonstrated that intermolecular exchange occurs between beta-sites, and another goal of this proposal is to elucidate the mechanistic and kinetic details of this metal exchange phenomenon.