Fig. 1: Compound heterozygous Dph1 mutations from a DEDSSH patient cause reduced eEF2 diphthamide modification. | Nature Communications

Fig. 1: Compound heterozygous Dph1 mutations from a DEDSSH patient cause reduced eEF2 diphthamide modification.

From: Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects

Fig. 1

T1(a) and T2 (b) weighted images of brain magnetic resonance imaging showing hypomyelination of bilateral frontal lobes and clear septum cyst. c, d Validation of DPH1 mutations in the proband and her immediate family members by Sanger sequencing. Encoded amino acid sequences are shown at the bottom. e Pedigree diagram showing the mutations in DPH1 within the proband’s family (black arrow indicates the proband). Western blotting detected total eEF2 (f), diphthamide-modified eEF2 (g), and total DPH1 (h) in lymphoblastoid cell lysates from the sister (s), proband (p), father (f) and mother (m). Representative blots are shown at the top, and quantification of four independent experiments is summarized in the lower graphs. Values in (f, g, and h) represent means ± SEM, and statistical significance was determined by unpaired t tests with two-sided analysis. i Sequence alignment showing the conservation of Glu242 (highlighted) and the surrounding residues in eukaryotic DPH1 proteins. j AlphaFold model of the active site of human DPH1 (cyan) in complex with archaeal EF2 (brown) based on PDB 6Q2D. Note the positions of Glu242 and Arg349. Distances between residues are in Å. k Sequence alignment showing the conservation of Arg349 (highlighted) and the surrounding residues in eukaryotic DPH1 and archaeal DPH2.

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