In silico analysis of RB and hepatocyte growth factor receptor
(MET) mutant proteins
The p.(Gln850Ter) mutation of RB protein causes a truncation of the
full-length protein (1-928) by 78 residues (Figure 3 ). The
deletion of the C-terminal region (851-928 residues) was predicted to
cause no alteration of the secondary structural arrangement, neither
local nor long-distance effect were predicted for the truncated protein.
Disorder prediction also showed that the truncation of the protein does
not cause significant changes in pathogenicity.
Neither secondary structure nor disorder predictions showed any adverse
effects of the deletion on protein structure. Therefore, the consequence
of the truncation can be associated with the loss of functional regions.
The functional importance of the C-terminal region in RB protein is
implied by the presence of ELMs, including a bipartite nuclear
localization signal (860-876). Consequently, the loss of this signal
sequence may result an impaired nuclear localization of the
mutant/truncated protein, while the wild-type protein naturally enters
the nucleus. The structure and possible interactions of RB1 protein was
presented in Figure 3 . The following coordinate files were used
to prepare the figure: 2QDJ.pdb [14]; 4ELL.pdb [15]; 2AZE.pdb
[16]; 3N5U.pdb [17]; 1H25.pdb [18]; 1PJM [19].
The p.(Thr1010Ile) mutation of MET protein causes a non-synonymous
mutation of a polar threonine to a hydrophobic isoleucine residue. The
possible effects of this point mutation were predicted by multiple
algorithms which showed no alteration of the secondary structural
arrangement at or in the proximity of the mutated residue, the disorder
propensity predicted for the mutant were highly similar to those
obtained for the wild-type. In agreement with this, the sequence-based
prediction of stability changes also implied neutral nature of the
mutation (-0.37 kcal/mol). We predicted no significant increase or
decrease of free energy change value upon p.(Thr992Ile) mutation.
Similar to RB protein, no local or global disturbances of the structure
could be predicted, rather functional changes of the residue in
992th position may be responsible for the phenotypic
effects.