14-3-3蛋白结合需要人源半胱天冬酶-2在S139和S164位点的磷酸化。
Human procaspase-2 phosphorylation at both S139 and S164 is required for 14-3-3 binding.
作者信息
Kalabova Dana, Smidova Aneta, Petrvalska Olivia, Alblova Miroslava, Kosek Dalibor, Man Petr, Obsil Tomas, Obsilova Veronika
机构信息
Department of Structural Biology of Signaling Proteins, Division BIOCEV, Institute of Physiology of the Czech Academy of Sciences, Prumyslova 595, 252 50 Vestec, Czech Republic; 2nd Faculty of Medicine, Charles University, V Uvalu 84, 15006 Prague, Czech Republic.
Department of Structural Biology of Signaling Proteins, Division BIOCEV, Institute of Physiology of the Czech Academy of Sciences, Prumyslova 595, 252 50 Vestec, Czech Republic.
出版信息
Biochem Biophys Res Commun. 2017 Nov 18;493(2):940-945. doi: 10.1016/j.bbrc.2017.09.116. Epub 2017 Sep 21.
Procaspase-2 phosphorylation at several residues prevents its activation and blocks apoptosis. This process involves procaspase-2 phosphorylation at S164 and its binding to the scaffolding protein 14-3-3. However, bioinformatics analysis has suggested that a second phosphoserine-containing motif may also be required for 14-3-3 binding. In this study, we show that human procaspase-2 interaction with 14-3-3 is governed by phosphorylation at both S139 and S164. Using biochemical and biophysical approaches, we show that doubly phosphorylated procaspase-2 and 14-3-3 form an equimolar complex with a dissociation constant in the nanomolar range. Furthermore, our data indicate that other regions of procaspase-2, in addition to phosphorylation motifs, may be involved in the interaction with 14-3-3.
半胱天冬酶原-2在多个位点的磷酸化可阻止其激活并阻断细胞凋亡。这一过程涉及半胱天冬酶原-2在S164位点的磷酸化及其与支架蛋白14-3-3的结合。然而，生物信息学分析表明，14-3-3结合可能还需要第二个含磷酸丝氨酸的基序。在本研究中，我们发现人半胱天冬酶原-2与14-3-3的相互作用受S139和S164位点磷酸化的调控。通过生化和生物物理方法，我们发现双磷酸化的半胱天冬酶原-2和14-3-3形成了一个解离常数在纳摩尔范围内的等摩尔复合物。此外，我们的数据表明，除了磷酸化基序外，半胱天冬酶原-2的其他区域可能也参与了与14-3-3的相互作用。
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