Fig. 4: Inhibitory loop of MIDEAS. | Nature Communications

Fig. 4: Inhibitory loop of MIDEAS.

From: A de novo missense variant in MIDEAS results in increased deacetylase activity of the MiDAC HDAC complex causing a neurodevelopmental syndrome

Fig. 4

a Alignment of the homologous proteins TRERF1, MIDEAS and ZNF541 to show the conserved regions N-terminal to the ELM2-SANT domains. T628-R635 is shown in yellow. P652-F671 is shown in cyan. The ELM2-SANT domain is shown in brown. Y654 is shown in magenta. b MIDEAS (coloured based on the alignment) shown as a cartoon and sticks completely wraps around HDAC1 (grey) shown as a surface with a closeup of the conserved N-terminal regions of MIDEAS. c Graphical representation of mass spectrometry analysis of peptides from Y654S MIDEAS and a bar chart showing the level of phosphorylation of either the serine or threonine in the STP sequence with (n = 2) and without (n = 3) the kinase inhibitor flavopiridol. Phosphorylation sites are shown as P in a purple box. STP is highlighted with a blue arrow. d Peaks obtained by deacetylation of a H3K9ac peptide in a time course over 2000 secs coloured blue to violet. e Initial rates of reaction calculated for MIDEAS complex with MIDEAS 628-887(YTP) WT, MIDEAS 717-887 (WT), MIDEAS 628-887 Y654S (STP), MIDEAS 628-887 Y654S T655A (SAP) and MIDEAS 628-887 Y654S T655D (SDP). Source data are provided as a Source Data file.

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