Table 1 Summary of wild-type and mutant hMLKL properties
hMLKL mutation | Location | Liposome permeabilization –ATP/+ATP | ATP-binding Kd (±SEM; μM) | Necroptotic killing function | Tumor association |
|---|---|---|---|---|---|
Nil (wild type) | +++/++ | 36 ± 4 | + | – | |
K230M | PsK β3 strand | ++/++ | – | Delayed | K230Q in colon carcinoma |
K255A/K256A | PsK αC helix | +++/++ | ND | + | – |
E258K | PsK αC helix | +/+ | 24 ± 2 | Delayed | E258K in colon and endometrial carcinomas19 |
G330E | PsK catalytic loop | +/+ | 28 ± 6 | Delayed | G330E melanoma; G330R endometrial carcinoma19 |
K331N | PsK catalytic loop | +++/+++ | – | + | – |
E351K | PsK activation loop | +/++ | 26 ± 6 | Delayed | E351K lung carcinoma19; E351Q prostate adenocarcinoma |
K354A/T355A | PsK activation loop | +++/+++ | − | ND | − |
T357E/S358E | PsK activation loop | +++/+++ | 56 ± 8 | − | − |
K16A/R17A | 4HB α1 helix | +/+ | ND | Delayed | R17W in endometrial cancer19 |
D107A/E111A | 4HB α4 helix | +++/++ | 23 ± 2 | − | − |
K157A | Brace helices | ++/++ | 164 ± 31 | Delayed | − |
