Fig. 8: Crystal structure and DDMPs of BAD SAHB 4.2 in complex with R129L-mutant BCL-2. | Nature Communications

Fig. 8: Crystal structure and DDMPs of BAD SAHB 4.2 in complex with R129L-mutant BCL-2.

From: Structural insights into chemoresistance mutants of BCL-2 and their targeting by stapled BAD BH3 helices

Fig. 8

Structure of the BCL-2ΔLΔC R129L/BAD SAHB 4.2 complex (a, PDB 9O16) demonstrates how replacement of the positively-charged R129 residue with leucine extends the hydrophobic groove, enabling further reinforcement of hydrophobic interactions with the all-hydrocarbon staple (b). DDMP comparing the BCL-2ΔLΔC R129L/BAD SAHB 4.2 and BCL-2ΔLΔC WT/BAD SAHB 4.2 protein complexes (PDB 9O16, 9O14) (c), with prominent differences in intra-protein proximities mapped onto the structure of BCL-2ΔLΔC R129L (d, PDB 9O16). e DDMP comparing the distances between BAD SAHB 4.2 residues and those of BCL-2ΔLΔC in the BCL-2ΔLΔC R129L/BAD SAHB 4.2 and BCL-2ΔLΔC WT/BAD SAHB 4.2 complexes. f Superposition of the two complexes (PDB 9O16, 9O14) highlights the impact of R129L mutagenesis on the position of the staple and associated peptide backbone at the hydrophobic groove. Source data are provided as a Source Data file.

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