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

The crystal structure of the homotetramer of a chimera beta alpha-subunit o f human hemoglobin was refined at 2.5 Angstrom resolution. The chimera subu nit was constructed by replacing an exon-encoded module M4 of the beta-subu nit with that of the alpha-subunit, simulating an exon-shuffling event. The implanted module M4 retained the native alpha-subunit structure, while mod ule M3 was disturbed around the site where a new type of intron was recentl y found. Some of the residues were found in alternative conformations that avoid steric hindrance at the subunit interface. The modules are modestly r igid in their backbone structures by using side-chains to compensate for in terface incompatibility. (C) 1999 Academic Press.