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This solution NMR structure of the EGFR TM dimer in detergent micelles provides the first view of an alternative (C-terminal) packing mode that has long been suspected to participate in stabilization of the inactive kinase conformation in non-ligand-bound receptor dimers.
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HER2 was the first EGFR-family TM dimer structure to be determined and provided the model for what is believed to represent the active state of the catalytically competent family members. The new solution NMR structure reported here includes the JM sequence and reveals what may be an alternative inactive conformation of HER2.
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The solution NMR structure of the FGFR3 TM dimer in detergent micelles features an unusual interface involving close glycine packing, aliphatic contacts and aromatic π–π stacking. A signalling mechanism is proposed wherein this structure represents the unliganded dimer conformation.
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The solution NMR structure of VEGFR2 TM domains in detergent micelles is presented with analysis of engineered glutamic acid mutants that result in constitutive receptor activation. A model based on simulations is proposed for switching between inferred active and inactive TM conformations.
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