Solid-State Deuterium NMR Studies Reveal μs-ns Motions in the HIV-1 Transactivation Response RNA Recognition Site

摘要

The HIV-1 transactivation response (TAR) RNA provides a classic example of adaptive protein-RNA recognition and is of key importance for viral replication. Transcription of the HIV genome is dependent upon binding of the viral regulatory protein Tat at a three-nucleotide bulge linking two short helices comprising the TAR hairpin (Figure 1). The inherent flexibility of this bulge allows it to undergo a conformational transition upon binding of Tat protein or even of a single arginine, generating the structure required to form a specific protein-RNA complex. The structures of the free RNA and of the Tat- or arginine-bound RNA are known; how the RNA traverses the intervening conformational landscape is not. In order to understand how TAR functions, it is necessary to characterize the full range of motions accessible to this RNA. Such knowledge would provide mechanistic insight into how the conformational changes occur and how the dynamics information required for Tat binding is encoded in the TAR sequence.