Table 1. Connection of mutational effects to reaction rates.
| Protein | Mutation class | Proposed molecular effect | Proposed reaction rate effect | References |
|---|---|---|---|---|
| WspA | Amino acidsubstitutions 352–420 | Trimer-of-dimer formation, localisation of Wsp clusters,interaction with WspD |
Increase r3 | (O'Connor et al., 2012; Griswold et al., 2002 ) |
| WspA | Deletions A281-A308 | Disrupt demethylation by WspF | Decrease r2 | (McDonald et al., 2009) |
| WspC/D | Fusion of WspC and WspD | Increased methylation byWspC, blocking access of WspF | Increase r1, decrease r2 | |
| WspE | Response regulatory domain phosphorylation site | Disrupt phosphorylation of WspF | Decrease r6 | Homology model |
| WspF | Any disabling mutation | Loss of negative regulation by WspF by demethylation of WspA | Decrease r2 | (Bantinaki et al., 2007; McDonald et al., 2009) |
| WspR | Amino acid substitutionsand small deletion inlinker region betweenresponse regulator and DGC domain | Constitutive activationof DGC withoutphosphorylation.Effects on subcellular clustering or multimeric state. | Increase r5 | (Goymer et al., 2006; De et al., 2009; Huangyutitham et al., 2013) |
| AwsX | In frame loss of function mutations | Loss of negative regulation of AwsR |
Decrease r3 | (Malone et al., 2012) |
| AwsR | Amino acidsubstitutionstransmembranehelix, periplasmic domain | Disruption of interaction with AwsX | Decrease r3 | (Malone et al., 2012) |
| AwsR | Amino acid substitutionsHAMP linker domain | Changes in dimerization, packing of HAMP domainscausing constitutive activation | Increase r4 | (Parkinson, 2010; Malone et al., 2012) |
| AwsO | Amino acid substitutionsin between signal peptide and OmpA domain | Constitutive activation andsequestering of AwsX | Increase r2 | (McDonald et al., 2009; Malone et al., 2012; Xu et al., 2016) |
| MwsR | Amino acid substitutions and small in frame deletions in interfacebetween EAL and DGC domains |
Changes to interdomain interaction or dimerization leading to constitutive activation of DGC function | Decrease r2, increase r1 | Homology model, (McDonald et al., 2009) |
| MwsR | Amino acid substitutionsnear DGC active site | Loss of feedback regulationor changes to interdomain interaction | Decrease r2, increase r1 | Homology model, (McDonald et al., 2009) |