蛋白激酶结构域
受体酪氨酸激酶
领域(数学分析)
酪氨酸激酶
细胞质
细胞生物学
计算生物学
信号转导
激酶
受体蛋白酪氨酸激酶
生物物理学
生物
化学
生物信息学
计算机科学
生物化学
基因
数学
数学分析
突变体
作者
François Inizan,Myriam Hanna,Maxim Stolyarchuk,Isaure Chauvot de Beauchêne,Luba Tchertanov
标识
DOI:10.1038/s41598-020-62460-7
摘要
Abstract Receptor tyrosine kinases (RTKs) are key regulators of normal cellular processes and have a critical role in the development and progression of many diseases. RTK ligand-induced stimulation leads to activation of the cytoplasmic kinase domain that controls the intracellular signalling. Although the kinase domain of RTKs has been extensively studied using X-ray analysis, the kinase insert domain (KID) and the C-terminal are partially or fully missing in all reported structures. We communicate the first structural model of the full-length RTK KIT cytoplasmic domain, a crucial target for cancer therapy. This model was achieved by integration of ab initio KID and C-terminal probe models into an X-ray structure, and by their further exploration through molecular dynamics (MD) simulation. An extended (2-µs) MD simulation of the proper model provided insight into the structure and conformational dynamics of the full-length cytoplasmic domain of KIT, which can be exploited in the description of the KIT transduction processes.
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