Nature Structural Biology pp 685 - 690

Everybody's familiar with different blood types. Matching the wrong blood to a needy patient can give rise to an acute medical emergency. A paper in the September issue of Nature Structural Biology solves the mystery of how the distinct blood types A and B are generated by two almost identical proteins. It all comes down to a tiny structural difference between the two proteins.

The molecular nature of different blood types stems from specific sugar modifications on the surface of red blood cells. Although blood types were identified more than 100 years ago, the two genes responsible for these modifications were isolated only in 1990. And, considering the life-threatening nature of blood type mismatches, the resulting proteins are surprisingly similar. The protein that imparts the A blood type differs by only four critical amino acids (out of a possible 354) from the protein responsible for blood type B. Using X-ray crystallography, Stephen Evans and collaborators identify a crucial amino acid that allows the proteins to make the distinct sugar modifications. After millennia of experimentation with 'humors', bloodletting and transfusions, this finding reveals that blood types are a matter of a small structural difference.