Insulin receptor family refers to receptor tyrosine kinases and consists of three proteins: insulin receptor (IR), type-1 insulin-like growth factor receptor (IGF-1R) and insulin receptor-related receptor (IRR). These proteins are important research objects due to interruptions of normal signaling may result to pathological conditions and developmental disabilities. Studies of these receptors activation dynamics is difficult due to necessary consideration of membrane environment for their correct organization and functioning. Nowadays there is no global theory about the activation mechanism of this family tyrosine kinases but importance of transmembrane (TM) domain dimerization in activation process was suggested. In this study we elaborated molecular models of TM domain dimers of IR, IGF-1R, IRR, and structural properties of these models were analyzed in silico. The resulting models can be used for study the role of membrane environment and point mutations on dimers stability and therefore receptor’s activity.
insulin receptor, transmembrane domain, molecular dynamics, alpha-helices interaction
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