1M5L

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

1M5L の概要

• エントリーDOI: 10.2210/pdb1m5l/pdb
• 分子名称: modified HIV-1 packaging signal stem-loop 1 RNA (1 entity in total)
• 機能のキーワード: base triplet, hiv, internal loop, packaging signal, sl-1, s-turn, rna
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12381.42

構造登録者

Gallego, J.,Greatorex, J.,Varani, G.,Lever, A. (登録日: 2002-07-09, 公開日: 2002-09-18, 最終更新日: 2024-05-22)

主引用文献

Greatorex, J.,Gallego, J.,Varani, G.,Lever, A.
Structure and stability of wild-type and mutant RNA internal loops from the SL-1 domain of the HIV-1 packaging signal
J.Mol.Biol., 322:543-557, 2002

PubMed Abstract: 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.

PubMed: 12225748
DOI: 10.1016/S0022-2836(02)00776-3

実験手法

SOLUTION NMR