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Article Dans Une Revue Scientific Reports Année : 2020

The First 3D Model of the Full-Length KIT Cytoplasmic Domain Reveals a New Look for an Old Receptor

Résumé

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 systematically 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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Dates et versions

hal-03000379 , version 1 (11-11-2020)

Identifiants

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François Inizan, Myriam Hanna, Maxim Stolyarchuk, Isaure Chauvot de Beauchêne, Luba Tchertanov. The First 3D Model of the Full-Length KIT Cytoplasmic Domain Reveals a New Look for an Old Receptor. Scientific Reports, 2020, ⟨10.1038/s41598-020-62460-7⟩. ⟨hal-03000379⟩
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