Table 2.
Residue | Number of MQ-Cys conjugatesa | Location | Effects and significance | |
---|---|---|---|---|
DNA-free p53 | DNA-bound p53 | |||
C124 | 0 | 5 | C-terminus of L1 loop | MQ-C124 is not resolved in the DNA-free structures because of limited accessibility of C124 to MQ. MQ-C124 is observed in p53-DNA tetramers, forming stabilizing interactions, and is highly significant in reinforcing the inter-dimer interface. |
C182 | 5 | 0 | L2 loop | MQ-C182 is observed in the DNA-free structures, depending on an outward L2 conformation, supported by MQ interactions with an adjacent p53 monomer in the crystal structures and hence its effect on p53 stability is not clear. |
C229 | 7 | 9 | C-terminus of S7/S8 loop | MQ-C229 is observed in both DNA-free and DNA-bound structures, forming stabilizing interactions. Enhanced MQ-mediated stabilization is observed in the p53-DNA tetramers, reinforcing the inter-dimer interface. |
C273 | 8 | N/Ab | C-terminus of S10 strand | MQ-C273 is observed in all p53 monomers of the MQ-modified R273C structures, showing similar patterns of extensive intramolecular stabilization. MQ-C273 is likely compatible with DNA binding. |
C275 | 3 | 0 | S10/H2 link | MQ-C275 is observed in the DNA-free structures forming stabilizing interactions. This MQ modification is likely incompatible with DNA binding. |
C277 | 4 | 10 | N-terminus of H2 helix | MQ-C277 is observed in both DNA-free and DNA-bound structures, forming stabilizing interactions. The MQ-mediated effect is highly significant in supporting the p53-DNA interface of the tetrameric complexes. |
aBased on the resolved MQ-Cys conjugates shown in Table 1.
bN/A stands for “Not Applicable”.