Crystal structure of a protein with an artificial exon-shuffling, module M4-substituted chimera hemoglobin βα, at 2.5 Å resolution

The crystal structure of the homotetramer of a chimera βα-subunit of human hemoglobin was refined at 2.5 Å resolution. The chimera subunit was constructed by replacing an exon-encoded module M4, of the β-subunit with that of the α-subunit, simulating an exon-shuffling event. The implanted module M4 retained the native α-subunit structure, while module M3 was disturbed around the site where a new type of intron was recently found. Some of the residues were found in alternative conformations that avoid steric hindrance at the subunit interface. The modules are modestly rigid in their backbone structures by using side-chains to compensate for interface incompatibility.