TYROSINE SULFATION OF CHEMOKINE RECEPTORS

趋化因子受体的酪氨酸硫酸化

• 批准号: 7722203
• 负责人: THOMAS P SAKMAR
• 金额: $ 0.14万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722203
• 关键词: Affect; Binding; CCR5 gene; Capsid Proteins; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; HIV Envelope Protein gp120; HIV-1; Institution; Length; Ligands; Mediating; Modification; N-terminal; Pattern; Peptides; Research; Research Personnel; Resources; Role; Source; Tyrosine; United States National Institutes of Health; Virus Diseases; Work; chemokine; chemokine receptor; extracellular; protein-tyrosine sulfotransferase; receptor; receptor function; sulfation

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. CCR5 chemokine receptor is a known coreceptor of HIV1 entry. Sulfation of tyrosines at the extracellular N-terminal segment of CCR5 has been shown to mediate binding of the viral coat protein gp120. We recently elucidated the pattern and temporal sequence of tyrosine sulfation of a peptide corresponding to the N-terminus of CCR5 (Seibert C, Cadene M, Sanfiz A, Chait BT, Sakmar TP, Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence. Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11031-6.) So far little is known about the role of tyrosine sulfation in chemokine receptors function, or the generality of this modification. In particular, more work is needed to understand how tyrosine sulfation affects the receptor's ability to bind its natural chemokine ligands and to determine in which receptors it is critical to viral infection. To better understand these aspects of chemokine receptors function, we have undertaken the characterization of tyrosine sulfation in full-length CCR5 as well as other chemokine receptors.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 CCR5 趋化因子受体是 HIV1 进入的已知辅助受体。 CCR5 胞外 N 末端片段酪氨酸的硫酸化已被证明可介导病毒外壳蛋白 gp120 的结合。我们最近阐明了与 CCR5 N 末端相对应的肽酪氨酸硫酸化的模式和时间序列（Seibert C、Cadene M、Sanfiz A、Chait BT、Sakmar TP、酪氨酰蛋白磺基转移酶对 CCR5 N 末端肽的酪氨酸硫酸化 1 2 遵循离散模式和时间顺序。Proc Natl Acad Sci U S A. 2002。 Aug 20;99(17):11031-6.) 迄今为止，人们对酪氨酸硫酸化在趋化因子受体功能中的作用或这种修饰的普遍性知之甚少。特别是，需要做更多的工作来了解酪氨酸硫酸化如何影响受体结合其天然趋化因子配体的能力，并确定在哪些受体中它对病毒感染至关重要。为了更好地了解趋化因子受体功能的这些方面，我们对全长 CCR5 以及其他趋化因子受体中的酪氨酸硫酸化进行了表征。