Figure 8.

Perforin-2 haploinsufficiency results in the reduced ability of human phagocytes to kill intracellular bacteria. (A) A monomer of human Perforin-2 in its pre-pore conformation. The MACPF and P2 domains are depicted in light green and orange respectively. The carboxy-terminal region is shown in tan. Glycans attached to N185 and N269 are shown as space filling models. Also shown are the positions of deleterious missense (magenta) and nonsense (cyan) mutations (90, 91). Residue numbering is relative to relative to UniProt entry Q2M385 (https://www.uniprot.org/uniprot/Q2M385). (B) Killing of intracellular S. Typhimurium by neutrophils isolated from the blood of a donor carrying a heterozygous Y430* nonsense mutation or healthy controls. Relative bacterial colony forming units are reported as Log2 Fold Change = log2(CFU at time X) – log2(CFU at time initial). **P < 0.01 by 2way ANOVA. This figure was adapted from previously published work (91) under the CC BY 4.0 license. Molecular graphics were rendered with UCSF ChimeraX from PDB file 6U2J (http://www.rcsb.org/structure/6U2J) (21).