An RNA-Binding chameleon

The arginine-rich RNA binding motif is found in a wide variety of proteins, including several viral regulatory proteins. Although related at the prima ry sequence level, arginine-rich domains from different proteins adopt diff erent conformations depending on the RNA site recognized, and in some cases fold only in the context of RNA. Here we show that the RNA binding domain of the Jembrana disease virus (JDV) Tat protein is able to recognize two di fferent TAR RNA sites, from human and bovine immunodeficiency viruses (HIV and BIV, respectively), adopting different conformations in the two RNA con texts and using different amino acids for recognition. In addition to the c onformational differences, the JDV domain requires the cyclin T1 protein fo r high-affinity binding to HIV TAR, but not to BIV TAR. The "chameleon-like " behavior of the JDV Tat RNA binding domain reinforces the concept that RN A molecules can provide structural scafolds for protein folding, and sugges ts mechanisms for evolving distinct RNA binding specificities from a single multifunctional domain.