蛋白质酶体消化模式的定量预测
Towards quantitative prediction of proteasomal digestion patterns of proteins
摘要：
我们讨论蛋白质的蛋白酶体降解问题。虽然蛋白酶体对细胞代谢的各个方面都很重要，但该过程的物理机制的一些细节仍然未知。我们介绍了一个随机模型的蛋白质降解的蛋白质，占蛋白质易位和拓扑结构的定位切割中心的蛋白酶体从第一原则。对于这个模型，我们开发的数学描述的基础上的主方程和技术重建固有的蛋白质和蛋白酶体的易位率，这是一个属性的蛋白酶体物种的裂解特异性，从质谱数据的消化模式。这些属性的确定，可以定量预测新的实验装置的消化模式。此外，我们设计了一个实验装置的合成多肽与周期性序列的氨基酸，这使得特别可靠的测定易位率。
英文摘要：
We discuss the problem of proteasomal degradation of proteins. Though proteasomes are important for all aspects of the cellular metabolism, some details of the physical mechanism of the process remain unknown. We introduce a stochastic model of the proteasomal degradation of proteins, which accounts for the protein translocation and the topology of the positioning of cleavage centers of a proteasome from first principles. For this model we develop the mathematical description based on a master-equation and techniques for reconstruction of the cleavage specificity inherent to proteins and the proteasomal translocation rates, which are a property of the proteasome specie, from mass spectroscopy data on digestion patterns. With these properties determined, one can quantitatively predict digestion patterns for new experimental set-ups. Additionally we design an experimental set-up for a synthetic polypeptide with a periodic sequence of amino acids, which enables especially reliable determination of translocation rates.
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