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Conformational Dynamics and Functional Implications of Phosphorylated β-Arrestins.
Structure ( IF 4.4 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.str.2019.12.008 Hyunook Kang 1 , Han-Sol Yang 2 , Ah Young Ki 2 , Seung-Bum Ko 1 , Kwon Woo Kim 2 , Chang Yong Shim 2 , Kiae Kim 2 , Hee-Jung Choi 1 , Ka Young Chung 2
Structure ( IF 4.4 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.str.2019.12.008 Hyunook Kang 1 , Han-Sol Yang 2 , Ah Young Ki 2 , Seung-Bum Ko 1 , Kwon Woo Kim 2 , Chang Yong Shim 2 , Kiae Kim 2 , Hee-Jung Choi 1 , Ka Young Chung 2
Affiliation
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Arrestins desensitize and/or internalize G-protein-coupled receptors by interacting with phosphorylated receptors. A few studies have reported that arrestins themselves can be phosphorylated, and the phosphorylation status modulates their cellular functions. However, the effects of phosphorylation on arrestin structure have not been studied. Here, we investigated the conformational changes in β-arrestin-1 and -2 upon incorporation of phospho-mimetic mutations into the known phosphorylation sites (i.e., S412D for β-arrestin-1 and S14D, T276D, S14D/T276D, S361D, T383D, and S361D/T383D for β-arrestin-2) by using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS analysis suggested that β-arrestin-2 S14D/T276D shows an HDX profile similar to the pre-active states, resulting in increased interaction with receptors. Phospho-mimetic mutation at corresponding residues of β-arrestin-1 (i.e., S13D/T275D) induced similar conformational and functional consequences, and the detailed structural changes related to β-arrestin-1 S13D/T275D were investigated further by X-ray crystallography.
中文翻译：
磷酸化β-Arrestins的构象动力学及其功能意义。
Arrestins通过与磷酸化受体相互作用来脱敏和/或内化G蛋白偶联受体。一些研究报告说，抑制蛋白本身可以被磷酸化，并且磷酸化状态调节它们的细胞功能。但是，尚未研究磷酸化对抑制蛋白结构的影响。在这里，我们研究了将磷酸模拟突变体掺入已知的磷酸化位点（即，S412D代表β-arrestin-1的S412D，T276D，S14D / T276D，S361D，T383D）时，β-arrestin-1和-2的构象变化，以及使用氢/氘交换质谱（HDX-MS）的S361D / T383D（用于β-arrestin-2）。HDX-MS分析表明，β-arrestin-2S14D / T276D显示出与活性前状态相似的HDX谱，导致与受体的相互作用增加。
更新日期：2020-01-13
中文翻译：
磷酸化β-Arrestins的构象动力学及其功能意义。
Arrestins通过与磷酸化受体相互作用来脱敏和/或内化G蛋白偶联受体。一些研究报告说，抑制蛋白本身可以被磷酸化，并且磷酸化状态调节它们的细胞功能。但是，尚未研究磷酸化对抑制蛋白结构的影响。在这里，我们研究了将磷酸模拟突变体掺入已知的磷酸化位点（即，S412D代表β-arrestin-1的S412D，T276D，S14D / T276D，S361D，T383D）时，β-arrestin-1和-2的构象变化，以及使用氢/氘交换质谱（HDX-MS）的S361D / T383D（用于β-arrestin-2）。HDX-MS分析表明，β-arrestin-2S14D / T276D显示出与活性前状态相似的HDX谱，导致与受体的相互作用增加。
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