1arj

From Proteopedia

Revision as of 13:45, 5 November 2007

ARG-BOUND TAR RNA, NMR

Overview

The human immunodeficiency virus type-1 (HIV-1) Tat protein stimulates, transcriptional elongation. Tat is introduced to the transcription, machinery by binding to the transactivation response region (TAR) RNA, stem-loop encoded by the 5' leader sequence found on all HIV-1 mRNAs. We, have used multidimensional heteronuclear NMR to determine the structure of, the TAR RNA in the presence of the ADP-1 polypeptide, a 37-mer that, carries the minimal RNA recognition region of the Tat protein and closely, mimics Tat binding specificity. In the presence of a variety of ligands, including ADP-1, related basic peptides and the amino acid derivative, argininamide, the bulge region of TAR undergoes a local conformational, rearrangement and forms a more stable structure. The structure of TAR in, the bound form has been determined from over 1000 NMR-derived constraints., The U23 residue at the 5' end of the bulge is positioned near G26 and A27, in the major groove, rather than stacked on A22 as in the free TAR. U23, and G26 are brought into close proximity by contacts to the guanidinium, group and side-chain amide group of a common arginine residue. However, the interaction of this guanidinium group with TAR is not the only source, of binding specificity. Besides NOEs to the arginine residue participating, in the conformational change, ADP-1 shows additional intermolecular NOEs, to TAR, suggesting that there are multiple points of contacts between TAR, RNA and residues from the basic and core regions of Tat. These structural, results provide important clues towards the identification of small, molecular mass and/or peptidomimetic inhibitors of the essential Tat-TAR, interaction.

About this Structure

1ARJ is a Protein complex structure of sequences from [1] with ARG as ligand. Structure known Active Site: TAR. Full crystallographic information is available from OCA.

Reference

The structure of the human immunodeficiency virus type-1 TAR RNA reveals principles of RNA recognition by Tat protein., Aboul-ela F, Karn J, Varani G, J Mol Biol. 1995 Oct 20;253(2):313-32. PMID:7563092

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