TYROSINE SULFATION OF CHEMOKINE RECEPTORS

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。 CCR5趋化因子受体是已知的HIV1进入的辅助受体。CCR5胞外N末端片段上酪氨酸的硫酸化已被证明介导了病毒外壳蛋白gp120的结合。我们最近阐明了CCR5 N-末端的酪氨酸硫化模式和时间序列(Seibert C，Cadene M，Sanfiz A，Chait BT，Sakmar TP，酪氨酸转硫酶1和2对CCR5 N-末端的酪氨酸硫化遵循离散模式和时间序列)。《学报》S A.2002.08.20；99(17)：11031-6.到目前为止，人们对酪氨酸硫化在趋化因子受体功能中的作用或这种修饰的一般性知之甚少。特别是，需要更多的工作来了解酪氨酸硫化如何影响受体结合其天然趋化因子配体的能力，并确定它在哪些受体上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，我们进行了全长CCR5和其他趋化因子受体中酪氨酸硫化的表征。

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.