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首页> 外文会议>Incorporating of the Australian Society for Biochemistry and Molecular Biology Combio >Defining the structural determinants of HIV-1 Nef that govern differential activation of Hck and Lyn tyrosine kinases
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Defining the structural determinants of HIV-1 Nef that govern differential activation of Hck and Lyn tyrosine kinases

机译：定义HIV-1 NEF的结构决定因素，治理HCK和LYN酪氨酸激酶的差异激活

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The human immunodeficiency virus (HIV) accessory protein Nef is a major determinant of HIV-1 pathogenicity and disease progression of Acquired Immunodeficiency Syndrome (AIDS). Since Nef has no catalytic activity, it exerts its pathological functions by binding and activating signaling proteins in host cells. Src-family tyrosine kinases Hck and Lyn are implicated to mediate some of the actions of Nef in infected host cells such as macrophages and B-lymphocytes. Src-family kinases contain several functional domains such as the SH3, SH2 and kinase domains that regulate the subcellular localization and kinase activity of Src-family kinases. In non-proliferating cells, Src-family kinases are mostly kept in the inactive state by two endogenous inhibitory tyrosine kinases CSK and CHK. Both CSK and CHK phosphorylate the consensus C-terminal regulatory tyrosine (Y_T) in Src-family kinases. Upon Y_T phosphorylation, Src-family kinases adopt an inactive conformation stabilized by two intramolecular inhibitory interactions - (i) the pY_T-SH2 interaction in which the phospho-Y_T binds the SH2 domain and (ii) the linker-SH3 interaction in which the SH2-kinase linker binds the SH3 domain. In this research project we aimed at deciphering how HIV-1 Nef activates Hck and Lyn.
机译：人类免疫缺陷病毒（HIV）辅助蛋白NEF是获得的免疫缺陷综合征（艾滋病）的HIV-1致病性和疾病进展的主要决定因素。由于NEF没有催化活性，因此通过在宿主细胞中结合和激活信号蛋白来施加病理功能。 SRC-Family酪氨酸激酶Hck和Lyn涉及介导NEF在受感染的宿主细胞中的一些作用，例如巨噬细胞和B淋巴细胞。 SRC-Family激酶含有几个功能域，例如SH3，SH2和激酶结构域，其调节SRC-Family激酶的亚细胞定位和激酶活性。在非增殖细胞中，SRC-Family激酶主要通过两个内源性抑制酪氨酸激酶CSK和CHK保持在无活性状态。 CSK和CHK均在SRC-Family激酶中磷酸化C-末端调节酪氨酸（Y_T）。在Y_T磷酸化上，SRC-族激酶采用由两个分子内抑制相互作用稳定的无活性构象 - （i）磷酸-Y_T结合SH2结构域的PY_T-SH2相互作用和（ii）其中SH2的连接器-SH3相互作用-kinase链接器绑定SH3域。在本研究项目中，我们旨在解密HIV-1 NEF如何激活HCK和LYN。

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