Studies have shown that peptides placed in different frameworks can adopt different conformations. The RNA-binding domain of JDV (Jembrana Disease Virus) Tat protein is able to recognize four different RNA sites adopting two different conformations. Mutagenesis experiments and NMR data provide evidence that the JDV Tat arginine-rich domain binds the TAR hairpins of JDV and BIV (Bovine Immunodeficiency Virus) in a b-hairpin conformation, while the different amino acid requirements and the cyclin T1 dependence for high affinity complex for the recognition of the TAR hairpin of HIV (Human Deficiency Virus) strongly suggest that the JDV domain does not adopt a discrete conformation in this RNA context. The JDV Tat peptide has an arginine-rich RNA-binding domain very similar to that of BIV Tat and the same arginines required for BIV Tat binding to BIV TAR are also crucial for JDV Tat binding in its b-hairpin conformation. Yet, mutant peptides show that the Tat peptide may make different contacts to the RNA compared to BIV Tat. Moreover, JDV TAR has a bulge architecture different from BIV TAR that has been shown to be crucial for Tat binding. We are currently studying the effects of these differences on the JDV TAR/Tat interaction.
Cheng AC, Calabro V, Frankel AD. Design of RNA-binding proteins and ligands. Curr Opin Struct Biol. 2001 Aug;11(4):478-84.
Campisi DM, Calabro V, Frankel AD. Structure-based design of a dimeric RNA-peptide complex. EMBO J. 2001 Jan 15;20(1-2):178-86.
Smith CA, Calabro V, Frankel AD. An RNA-binding chameleon. Mol Cell. 2000 Nov;6(5):1067-76.
Calabro V, Sabatier JM, Blanc E, Lecomte C, Van Rietschoten V, Darbon H. Differential involvement of disulfide bridges on the folding of a scorpion toxin. J Pept Res. 1997 Jul;50(1):39-47.