Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model

Figure 2

(a) The complex between IFNγ and the extracellular part of its receptor 1 (IFNγR1) from crystal structure of PDB code 1fg9 [19]. The two IFNγR1 molecules are drawn as blue cartoon and IFNγ homodimer as yellow cartoon. The eight identified cavities in the receptor molecule are shown as numbered red surfaces. (b) A close-up of the mutated cavities. The receptor cavities are drawn as red surface and residues selected for mutations as red sticks; valine 35 is labeled. (c) Residue conservancy calculated by strict alignment of 32 sequences of the extracellular part of IFNγR1 from 19 species. The residues lining the cavities and not suitable for mutation are highlighted in green, those selected by FoldX as mutable in yellow, and the residues selected for mutations after MD simulations are in red (they are also listed in Table 1). Blue highlights show IFNγR1 mutants occurring naturally in humans. Percentages of the conservation are shown on the left and right sides; analyzed sequence (residues 6–245 of the UniProt entry P15260) is shown at the bottom of the alignment.

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