CRYSTAL STRUCTURE DETERMINATION OF M2 PROTON CHANNEL

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 甲型流感病毒的M2蛋白是病毒包膜的重要组成部分。它是一种pH激活的质子通道，对病毒复制至关重要。M2是一种含有97个氨基酸的蛋白质，具有一个单一的跨膜(TM)α-螺旋，它组装形成一个同质四聚体通道，是抗流感药物金刚烷胺和金刚乙胺的靶标。这些药物被预防性使用了30多年，然而，在过去的几年里，人类、鸟类和猪对这些药物的抗药性已达到90%以上。为了了解质子传导机制和为突变体设计有效的新药，最近，我们解决了蛋白质TM区的晶体结构(3.5分辨率)，并在存在和不存在通道阻滞剂(2.0分辨率)的情况下解决了这一问题。在我们的持续努力中，我们正在努力获得不同结构的野生型蛋白的高分辨率结构，无论有没有药物存在，以及耐药性突变。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The M2 protein from influenza A virus forms an essential component of viral envelope. It is a pH-activated proton channel and is crucial for viral replication. The M2 is a 97 amino acid protein with a single transmembrane (TM) alpha-helix, that assembles to form a homotetrameric channel and is the target of the ant-influenza drugs amantadine and rimantadine. These drugs were used prophylactically for over three decades, however, in the last few years resistance to these drugs in humans, birds, and pigs has reached over 90%. With an envision to understand the proton conduction mechanism and designing effective new drug for mutants, recently, we have solved the crystal structure of the TM region of protein ( at 3.5 resolution ) with and without presence of channel blocking drug (at 2.0 resolution). In our continuing effort, we are working towards obtaining high resolution structures of wild type protein of different constructs, with and without presence of drug, and drug resistance mutant.