1m5l

From Proteopedia

Revision as of 14:22, 15 February 2008

Structure of wild-type and mutant internal loops from the SL-1 domain of the HIV-1 packaging signal

Overview

The packaging signal (Psi) of the human immunodeficiency virus type 1, (HIV-1) enables encapsidation of the full-length genomic RNA against a, background of a vast excess of cellular mRNAs. The core HIV-1 Psi is, approximately 109 nucleotides and contains sequences critical for viral, genomic dimerisation and splicing, in addition to the packaging signal. It, consists of a series of stem-loops (termed SL-1 to SL-4), which can be, arranged in a cloverleaf secondary structure. Using a combination of NMR, spectroscopy, UV melting experiments, molecular modeling and phylogenetic, analyses, we have explored the structure of two conserved internal loops, proximal to the palindromic sequence of SL-1. Internal loop A, composed of, six purines, forms a flexible structure that is strikingly similar to the, Rev responsive element motif when bound to Rev protein. This result, suggests that it may function as a protein-binding site. The absolutely, conserved four-purine internal loop B is instead conformationally and, thermodynamically unstable, and exhibits multiple conformations in, solution. By introducing a double AGG to GGA mutation within this loop, its conformation is stabilised to form a new intra-molecular G:A:G, base-triplet. The structure of the GGA mutant explains the relative, instability of the wild-type loop. In a manner analogous to SL-3, we, propose that conformational flexibility at this site may facilitate, melting of the structure during Gag protein capture or genomic RNA, dimerisation.

About this Structure

1M5L is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

Structure and stability of wild-type and mutant RNA internal loops from the SL-1 domain of the HIV-1 packaging signal., Greatorex J, Gallego J, Varani G, Lever A, J Mol Biol. 2002 Sep 20;322(3):543-57. PMID:12225748

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