Liepe Juliane, Holzhütter Herman-Georg, Kloetzel Peter M, Stumpf Michael P H, Mishto Michele
Theoretical Systems Biology, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK.
Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Biomolecules. 2014 Jun 20;4(2):585-99. doi: 10.3390/biom4020585.
Proteasomes are key proteases involved in a variety of processes ranging from the clearance of damaged proteins to the presentation of antigens to CD8+ T-lymphocytes. Which cleavage sites are used within the target proteins and how fast these proteins are degraded have a profound impact on immune system function and many cellular metabolic processes. The regulation of proteasome activity involves different mechanisms, such as the substitution of the catalytic subunits, the binding of regulatory complexes to proteasome gates and the proteasome conformational modifications triggered by the target protein itself. Mathematical models are invaluable in the analysis; and potentially allow us to predict the complex interactions of proteasome regulatory mechanisms and the final outcomes of the protein degradation rate and MHC class I epitope generation. The pioneering attempts that have been made to mathematically model proteasome activity, cleavage preference variation and their modification by one of the regulatory mechanisms are reviewed here.
蛋白酶体是关键的蛋白酶，参与从清除受损蛋白质到向CD8 + T淋巴细胞呈递抗原等多种过程。目标蛋白内使用哪些切割位点以及这些蛋白的降解速度对免疫系统功能和许多细胞代谢过程有着深远影响。蛋白酶体活性的调节涉及不同机制，如催化亚基的替换、调节复合物与蛋白酶体门的结合以及由目标蛋白本身触发的蛋白酶体构象修饰。数学模型在分析中非常宝贵，并且可能使我们能够预测蛋白酶体调节机制的复杂相互作用以及蛋白质降解率和MHC I类表位产生的最终结果。本文综述了在蛋白酶体活性、切割偏好变化及其通过一种调节机制进行修饰的数学建模方面所做的开创性尝试。
