Structure solution of C-reactive proteins: molecular replacement with a twist.

The pentameric structure of C-reactive proteins (CRP) has been derived by a combination of automated and manual molecular-replacement techniques. The method is generally applicable to other multimeric assemblies. The highly homologous human serum amyloid P component (hSAP) structure fails to provide a pentameric molecular-replacement solution for CRP. In the absence of a significant signal from an individual protomer, the hSAP structure has been manually modified in terms of protomer assembly to provide the true pentameric model of CRP. The CRP protomers are rotated or twisted by 14 degrees about an axis, through the protomer centre, which is approximately perpendicular to the pentamer radius and the molecular fivefold axis. The results demonstrate clearly that protomers with very similar folds arising from high sequence homology need not necessarily be assembled together in the same way although the symmetry of the resulting oligomer may be maintained. In a curious twist the CRP structure which provided the general CRP model remains unsolved, while the model itself has so far provided the solution of two other CRP structures.