Table 2.
Rate constants for all reactions in the necroptosis model
| Parameter | Reaction | Medians | Units |
|---|---|---|---|
| P1 | R1: association of TNF to TNFR | 10 [1.07, 0.39, 0.91, 0.49] | μM−1 min−1 |
| P2 | R2: dissociation of TNF:TNFR | 10 [−2.00, −2.22, −3.40, −2.20] | min−1 |
| P3 | R3: degradation of TNF | 10 [−1.52, −1.70, −1.62, −1.62] | min−1 |
| P4 | R4: association of TRADD to complex I | 10 [0.11, 0.45, 0.71, 1.19] | μM−1 min−1 |
| P5 | R5: dissociation of TRADD from complex I | 10 [1.22, 1.51, 1.84, 1.30] | min−1 |
| P6 | R6: association of RIP1-u to complex I | 10 [6.30, 5.91, 6.19, 5.94] | μM−1 min−1 |
| P7 | R7: dissociation of RIP1-u from complex I | 10 [−1.70, −1.82, −1.70, −1.70] | min−1 |
| P8 | R8: association of TRAF2 to complex I | 10 [5.34, 5.51, 5.22, 5.16] | μM−1 min−1 |
| P9 | R9: dissociation of TRAF2 from complex I | 10 [−2.26, −1.82, −2.40, −1.70] | min−1 |
| P10 | R10: association of cIAP to complex I | 10 [4.70, 4.58, 4.63, 4.57] | μM−1 min−1 |
| P11 | R11: dissociation of cIAP from complex I | 10 [−0.01, −0.33, −0.05, −0.24] | min−1 |
| P12 | R12: ubiquitination of RIP1-u by cIAP in complex I | 10 [−1.52, −2.00, −2.00, −1.70] | min−1 |
| P13 | R13: association of LUBAC to RIP1-Ub in complex I | 10 [2.41, 2.01, 2.12, 2.42] | μM−1 min−1 |
| P14 | R14: dissociation of LUBAC from RIP1-Ub in complex I | 10 [−3.80, −3.74, −4.44, −3.74] | min−1 |
| P15 | R15: association of A20 to RIP1-Ub in complex I | 10 [4.88, 4.05, 5.18, −0.43] | μM−1 min−1 |
| P16 | R16: dissociation of A20 from complex I | 10 [−1.40, −2.00, −2.00, −4.05] | min−1 |
| P17 | R17: association of CYLD to RIP1-Ub in complex I | 10 [7.62, 1.84, 7.43, 1.71] | μM−1 min−1 |
| P18 | R18: dissociation of CYLD from complex I | 10 [0.28, 0.11, 0.59, 0.71] | min−1 |
| P19 | R19: deubiquitination of RIP1-Ub by A20 in complex I | 10 [−1.52, −1.00, −1.10, −1.52] | min−1 |
| P20 | R20: deubiquitination of RIP1-Ub by CYLD in complex I | 10 [−1.22, 2.67, 2.84, 2.59] | min−1 |
| P21 | R21: association of FADD to RIP1-u:TRADD in complex II | 10 [7.47, 7.73, 7.53, 7.37] | μM−1 min−1 |
| P22 | R22: dissociation of FADD from RIP1-u:TRADD in complex II | 10 [−0.17, −0.15, −0.31, −0.10] | min−1 |
| P23 | R23: association of C8i to FADD in complex IIa | 10 [1.49, 1.48, 1.49, 1.15] | μM−1 min−1 |
| P24 | R24: dissociation of C8i from complex IIa | 10 [−2.10, −2.10, −2.00, −1.72] | min−1 |
| P25 | R25: association of FLIP to C8i in complex IIa | 10 [3.73, 3.85, 3.93, 3.72] | μM−1 min−1 |
| P26 | R26: dissociation of FLIP from C8i in complex IIa | 10 [−4.10, −4.70, −5.40, −3.96] | min−1 |
| P27 | R27: activation of C8i in complex IIa | 10 [−2.05, −2.30, −2.30, 1.66] | min−1 |
| P28 | R28: inactivation of C8a in complex IIa | 10 [1.41, 1.53, 1.36, −2.41] | min−1 |
| P29 | R29: degradation of RIP1-u by C8a:FLIP in complex IIa | 10 [−0.12, −0.38, −0.21, −0.10] | min−1 |
| P30 | R30: association RIP3 to RIP1-u in complex IIb | 10 [6.22, 6.10, 6.09, 6.26] | μM−1 min−1 |
| P31 | R31: dissociation of RIP3 from RIP1-u in complex IIb | 10 [−0.79, −0.81, −0.53, −0.97] | min−1 |
| P32 | R32: association of C8a:FLIP to complex IIb | 10 [3.28, 3.83, 3.18, 3.19] | μM−1 min−1 |
| P33 | R33: dissociation of C8a:FLIP from complex IIb | 10 [−3.00, −3.00, −2.21, −2.26] | min−1 |
| P34 | R34: degradation of RIP1-u by C8a:FLIP in complex IIb | 10 [−2.60, −2.40, −3.85, −1.75] | min−1 |
| P35 | R35: dissociation of RIP1-u:RIP3 from complex IIb | 10 [−3.30, −2.44, −2.42, −2.41] | min−1 |
| P36 | R36: phosphorylation of RIP1-p by RIP3 in the necrosome | 10 [−2.28, −2.14, −2.32, −2.31] | min−1 |
| P37 | R37: phosphorylation of RIP3 by RIP1-p in the necrosome | 10 [−2.62, −2.55, −2.61, −3.01] | min−1 |
| P38 | R38: association of MLKL to the necrosome | 10 [5.03, 4.16, 3.98, 4.11] | μM−1 min−1 |
| P39 | R39: dissociation of MLKL from the necrosome | 10 [0.29, 0.47, 0.02, 0.16] | min−1 |
| P40 | R40: phosphorylation of MLKL | 10 [2.10, 2.63, 2.46, 2.53] | min−1 |
C8i, C8a: inactive and active caspase-8; RIP1-u, RIP1-Ub, RIP1-p: unmodified, ubiquitinated, and phosphorylated RIP1; RIP3-p: phosphorylated RIP3. Median values are ordered as 10 [M1,M2,M3,M4].