Known allosteric proteins have central roles in genetic disease
Fig 6
Structural and dynamical characteristics of pathogenic mutations in allosteric and non-allosteric proteins.
A-B) Residue interaction matrix of Pfam domains of allosteric (A) and non-allosteric (B) proteins. C-D) The difference between the two matrices (panel C) shows that allosteric proteins have significantly fewer long-range interactions in their Pfam domains than non-allosteric proteins (panel D), and are likely to be more flexible. E-F) Disease associated mutations are significantly enriched in community interfaces, i.e. residues that interact with members of other communities, both in the case of allosteric and non-allosteric proteins. The enrichment is more pronounced for stronger interactions like H-bonds (panel E). G) The distribution of disease mutations across communities (horizontal bar) differs from the random expectation (violin plot) more in allosteric proteins than in non-allosteric ones, indicating that pathogenic mutations have a stronger effect in allosteric proteins. See also S9 Fig. H) Disease associated mutations are significantly enriched in the protein-protein interfaces of both allosteric and non-allosteric heteromers. I) A much less pronounced, but also significant enrichment is present in the interfaces of homomers. J) The structure of Mitogen-activated protein kinase 8 (MAPK8, PDB ID: 4qtd). K) Community structure of MAPK8. Each community is represented by a different colour, residue-residue interactions between different communities (community interfaces) are indicated with black.