Extended Data Table 1 |.
Estimates of Km and kobs for Substrate Ubiquitylation.
Substrate | E2 | CRL1β-TRCP | Km(10−9M) | kobsS0–S1 (sec−1) | kobsS1–S2 (sec−1) | kobsS0–S1/ Km (M−1sec−1) | Fold change |
---|---|---|---|---|---|---|---|
IκBα | WT UBE2D | NEDD8-CUL1–RBX1 | 408 ± 57 | 12.9 ± 1.7 | 0.24 ± 0.04 | 3.2 × 107 | - |
IκBα | WT UBE2D | CUL1–RBX1 | 4014 ±956 | 0.05 ± 0.002 | - | 1.2 × 104 | 2667 |
WT β-cat | WT UBE2D | NEDD8-CUL1–RBX1 | 214 ±30 | 4.8 ±0.46 | 0.19 ±0.02 | 2.2 × 107 | - |
WT β-cat | WT UBE2D | CUL1–RBX1 | 4638±138 | 0.05 ± 0.005 | - | 1.1 × 104 | 2000 |
medium β-cat | WT UBE2D | NEDD8-CUL1–RBX1 | 372 ± 48 | 11 ± 1.00 | 0.24 ± 0.04 | 3.0 × 107 | - |
medium β-cat | WT UBE2D | CUL1–RBX1 | 4875 ±1328 | 0.08 ± 0.005 | - | 1.6 × 104 | 1875 |
short β-cat | WT UBE2D | CUL1–RBX1 | 5207±1051 | 0.02 ± 0.0004 | - | 3.8 × 103 | |
medium β-cat | WT UBE2D | NEDD8 I44A-CUL1–RBX1 | 1087 ±69 | 3.60 ±0.27 | 0.17 ±0.03 | 3.3 × 106 | 9.1 |
medium β-cat | WT UBE2D | UB-CUL1–RBX1 | 2056 ±170 | 1.0 ±0.03 | 0.15 ±0.01 | 4.9 × 105 | 61.2 |
medium β-cat | WT UBE2D | NEDD8 Q40E-CUL1–RBX1 | 1941 ±226 | 1.77 ± 0.13 | 0.07 ±0.01 | 9.1 × 105 | 33.0 |
medium β-cat | WT UBE2D | UBylized NEDD8-CUL1–RBX1 | 1651±137 | 2.20 ±0.15 | 0.17 ±0.04 | 1.3 × 106 | 23.1 |
medium β-cat | S22R UBE2D | NEDD8-CUL1–RBX1 | 913 ±135 | 1.89 ±0.14 | 0.17 ±0.03 | 2.1 × 106 | 14.2 |
medium β-cat | S22R UBE2D | NEDD8 I44A-CUL1–RBX1 | 5190 ±604 | 0.13 ±0.01 | - | 2.5 × 104 | 1200 |
medium β-cat | S22R UBE2D | UB-CUL1–RBX1 | 6492 ± 872 | 0.08 ± 0.005 | - | 1.2 × 104 | 2500 |
medium β-cat | S22R UBE2D | CUL1–RBX1 | 4007 ± 754 | 0.013 ±0.002 | - | 3.3 ×103 | 9091 |
medium β-cat | S22R UBE2D | NEDD8 Q40E-CUL1–RBX1 | 3581 ± 367 | 0.17 ±0.005 | - | 4.7 × 104 | 638.3 |
medium β-cat | S22R UBE2D | UBylized NEDD8-CUL1–RBX1 | 6105 ±1030 | 0.12 ±0.007 | - | 2.0 × 104 | 1500 |
medium β-cat | H32A UBE2D | NEDD8-CUL1–RBX1 | 347 ± 53 | 8.15 ± 1.04 | 0.73 ± 0.09 | 2.3 × 107 | 1.3 |
medium β-cat | H32A UBE2D | NEDD8 I44A-CUL1–RBX1 | 3431 ± 332 | 0.58 ± 0.04 | 0.12 ±0.02 | 1.7 × 105 | 176.5 |
medium β-cat | H32A UBE2D | UB-CUL1–RBX1 | 2999 ± 301 | 0.34 ±0.01 | 0.10 ±0.02 | 1.1 × 105 | 272.7 |
medium β-cat | H32A UBE2D | CUL1–RBX1 | 3305 ±1119 | 0.06 ± 0.003 | - | 1.8 × 104 | 1666.7 |
medium β-cat | H32A UBE2D | NEDD8 Q40E-CUL1–RBX1 | 2923 ± 459 | 0.81 ±0.06 | - | 2.8 × 105 | 107.1 |
medium β-cat | H32A UBE2D | UBylized NEDD8-CUL1–RBX1 | 4303 ±310 | 0.28 ± 0.02 | - | 6.5 × 104 | 461.5 |
UB-β-cat | WT UBE2D | NEDD8-CUL1–RBX1 | 148 ± 15 | - | 0.48 ± 0.02 | ||
UB-β-cat | WT UBE2D | CUL1–RBX1 | 1503 ±439 | - | 0.005 ± 0.0004 |
S0 refers to unmodified substrate, S1 to substrate modified by a single UB, and S2 to substrate modified with two UBs. S0-S1 refers to the transition from unmodified to UB-substrate, and S1-S2 to the transition from UB-substrate to UB-UB-substrate. Values for Km are the best fit values derived from nonlinear regression in Prism, and value for kobs are the best fit values derived from nonlinear regression in Mathematica. The measure of error is the standard error as determined by Prism and Mathematica, respectively, from experiments and curve fits such as those shown in Extended Data Figure 1 (n=2).