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Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator
Biological Sciences Faculty Research
  • Erwann P. Loret
  • Philippe T. Georgel, Marshall University
  • W. Curtis Johnson, Jr.
  • Pui Shing Ho
Document Type
Conference Proceeding
Publication Date
10-1-1992
Abstract

Transcription in the human immunodeficiency virus type 1 (HIV-1) retrovirus is regulated by binding the viral Tat protein (trans-acting transcriptional activator) to the trans-activation response (TAR) RNA sequence. Here, vacuum UV circular dichroism (VUV-CD) is used to study the structure of TAR and its complex with two peptide fragments that are important for Tat binding to TAR. The VUV-CD spectrum of TAR is typical of A-form RNA and is minimally perturbed when bound to either the short or the long Tat peptide. The CD spectra ofthe complexes indicate an extended structure in the argnine-rich region of Tat from amino acid residue 47 through residue 58 and a short a-helix within the adjacent 59-72 region. Models of TAR and its peptide complexes are constructed to integrate these spectroscopic results with current biochemical data. The model suggests that (i) the arginine-rich 49-58 region is primarily responsible for electrostatic interactions with the phosphates of the RNA, (ii) the arginine side chains can additionally interact with substituent groups of the nucleotide bases to confer base recognition in the complex, (iii) the recognition of uracil-23 in TAR is facilitated by the peptide backbone, and (iv) the glutamine-rich face of an a-helix within the 59-72 region pairs to bases UGG at nucleotide positions 31-33 in the TAR loop and thus provides an additional motif in the Tat trans-activating protein to recognize TAR RNA.

Comments

The copy of record is at https://0-www.pnas.org.library.simmons.edu/content/pnas/89/20/9734.full.pdf.

Copyright © 1992 The Authors. All rights reserved.

Citation Information
Loret EP, Georgel P, Johnson WC, Ho PS. Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator. Proceedings of the National Academy of Sciences. 1992;89(20):9734-8.