STRUCTURAL STUDY OF DISEASE RELATED FACTORS

疾病相关因素的结构研究

• 批准号: 8361650
• 负责人: Yong Xiong
• 金额: $ 4.7万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361650
• 关键词: Antiviral Agents; C-terminal; Cysteine; Disease; Funding; Grant; HIV-1; Human; Length; Membrane Proteins; National Center for Research Resources; Positioning Attribute; Principal Investigator; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; Virus; alpha helix; cost; dimer; flexibility; insight; mutant; structural biology; Antiviral Agents; C-terminal; Cysteine; Disease; Funding; Grant; HIV-1; Human; Length; Membrane Proteins; National Center for Research Resources; Positioning Attribute; Principal Investigator; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; Virus; alpha helix; cost; dimer; flexibility; insight; mutant; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tetherin/BST2 is a type-II membrane protein that inhibits the release of a range of enveloped viruses, including HIV-1. We solved three crystal structures of human tetherin, including the full-length ectodomain, a triple cysteine mutant and an ectodomain truncation. These structures show that tetherin forms a continuous alpha helix encompassing almost the entire ectodomain. Tetherin helices dimerize into parallel coiled coils via interactions throughout the C-terminal portion of the ectodomain. A comparison of the multiple structures of the tetherin dimer reveals inherent constrained flexibility at two hinges positioned at residues A88 and G109. In the crystals, two tetherin ectodomain dimers associate into a tetramer by forming an antiparallel four-helix bundle at their N termini. This study provides detailed insight into the mechanisms by which this broad-spectrum antiviral restriction factor can function.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 Tetherin/BST2是一种II型膜蛋白，可抑制包括HIV-1在内的一系列包膜病毒的释放。我们解决了人类Tetherin的三个晶体结构，包括全长外生域，三重半胱氨酸突变体和胞外域截断。这些结构表明，Tetherin形成了几乎整个外域域的连续α螺旋。 Tetherin Helices通过整个c-末端部分的相互作用将平行的盘绕线圈二聚成螺旋线圈。 Tetherin二聚体的多个结构的比较表明，位于残基A88和G109处的两个铰链处的固有约束柔韧性。在晶体中，通过在其n末端形成反平行的四螺旋束，将两个系蛋白域二聚体关联到四聚体中。这项研究提供了对这种广谱抗病毒限制因素可以起作用的机制的详细见解。