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Fig. 3 | BMC Medical Genetics

Fig. 3

From: Germline activating MTOR mutation arising through gonadal mosaicism in two brothers with megalencephaly and neurodevelopmental abnormalities

Fig. 3

E1799K is a pathogenic activating mutation. a) Location of p.E1799K in relation to the domain/ structural organization of MTOR. Structural elements shown are the two groups of HEAT (Huntington Elongation Factor 3, A Subunit of PP2A TOR1) repeats; the FAT (FKBP12-Rapamycin-Associated Protein/TOR, Ataxia-Telangiectasia, Transactivation/ Transformation Domain-Associated Protein) domain; the FRB (FKBP12-Rapamycin Binding) domain; the KIN (Kinase) domain; and the terminal FATC (FAT C-Terminal) domain. b) The conservation plot reveals that E1799 (black rectangle) is evolutionarily conserved across vertebrates, which suggests that this amino acid plays an essential role for the normal function of MTOR kinase. c) A 3D schematic of the local environment surrounding the FAT-kinase domain interface that illustrates the mechanism by which p.E1799K causes hyperactivation of MTOR kinase. The FAT domain is represented in green while the kinase domain is peach-colored. Highlighted residues include E1799 (magenta stick), K1799 (white stick) and the activating residues described in the text: E2419, R1905 and R2505 (represented as sticks colored according to the domain in which they reside)

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BMC Medical Genetics

ISSN: 1471-2350

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