Biochemistry Seminar
"Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases"
Zoom Link:
https://notredame.zoom.us/j/93986155478?pwd=2g0Fbt5db1D4buI76ZNL5b47LShi6P.1
Meeting ID: 939 8615 5478
Passcode: 491966
Abstract: The activation mechanisms of the transmembrane glycoproteins insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) remain poorly understood. These receptors transmit signals across the membrane when extracellular peptide ligands bind, inducing structural changes in the extracellular subunits, leading to transmembrane domain (TMD) dimerization and tyrosine kinase autophosphorylation. To clarify the activation mechanism, the authors employed coarse-grained (CG) molecular dynamics simulations to study the dimerization propensity of IR and IGF1R TMDs. The simulations revealed that TMDs spontaneously dimerize and adopt distinct configurations. Specifically, IR TMDs predominantly formed X-shaped structures with asymmetric helical packing and a significant tilt relative to the membrane normal, while IGF1R TMDs adopted symmetric V-shaped or parallel configurations with little to no tilt. These findings provide new insights into the structural dynamics underlying IR and IGF1R activation without requiring structures of full-length receptors in apo or liganded states.