Globular protein backbone conformational disorder in crystal structures

Abstract

Proteins are not static molecules but dynamic entities able to modify their structure for several reasons, from the necessity to recognize partners to the regulation of their thermodynamic stability. Conformational disorder is frequent in protein structures and atoms can have, in protein crystal structures, two or more alternative, equilibrium positions close to each other. Here, a set of protein crystal structures refined at very high resolution (1 Å or better) is examined to characterize the conformational disorder of the backbone atoms, which is not infrequent: about 15% of the protein backbone atoms are conformationally disordered and three quarters of them have been deposited with two or more equilibrium positions (most of the others were not detected in the electron density maps). Several structural features have been examined and it was observed that Cα atoms tend to be disordered more frequently than the other backbone atoms, likely because their disorder is induced by disordered side chains: side-chain disorder is two times more frequent than backbone disorder. Surprisingly, backbone disorder is only slightly more frequent in loops than in helices and strands and this is in agreement with the observation that backbone disorder is a localized phenomenon: in about 80% of the cases, it is observed in one amino acid and not in its neighbors. However, although backbone disorder does not cluster along the polypeptide sequence, it tends to cluster in 3D, since backbone-disordered amino acids distant in sequence are close in the 3D space.