Reversible substrate-induced domain motions in ribonuclease A.

Despite the increasing number of successful determinations of complex protein structures the understanding of their dynamics properties is still rather limited. Using X-ray crystallography, we demonstrate that ribonuclease A (RNase A) undergoes significant domain motions upon ligand binding. In particular, when cytidine 2'-monophosphate binds to RNase A, the structure of the enzyme becomes more compact. Interestingly, our data also show that these structural alterations are fully reversible in the crystal state. These findings provide structural bases for the dynamic behavior of RNase A in the binding of the substrate shown by Petsko and coworkers (Rasmussen et al. Nature 1992;357:423-424). These subtle domain motions may assume functional relevance for more complex system and may play a significant role in the cooperativity of oligomeric enzymes. Copyright 2001 Wiley-Liss, Inc.