2gm0

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Linear dimer of stemloop SL1 from HIV-1

Overview

The packaging signal of HIV-1 RNA contains a stem-loop structure, SL1, which serves as the dimerization initiation site for two identical copies, of the genome and is important for packaging of the RNA genome into the, budding virion and for overall infectivity. SL1 spontaneously dimerizes, via a palindromic hexanucleotide sequence in its apical loop, forming a, metastable kissing dimer form. Incubation with nucleocapsid protein causes, this form to refold to a thermodynamically stable mature linear dimer., Here, we present an NMR structure of the latter form of the full-length, SL1 sequence of the Lai HIV-1 isolate. The structure was refined using, nuclear Overhauser effect and residual dipolar coupling data. The, structure presents a symmetric homodimer of two RNA strands of 35, nucleotides each; it includes five stems separated by four internal loops., The central palindromic stem is surrounded by two symmetric adenine-rich, 1-2 internal loops, A-bulges. All three adenines in each A-bulge are, stacked inside the helix, consistent with the solution structures of, shorter SL1 constructs determined previously. The outer 4-base pair stems, and, proximal to them, purine-rich 1-3 internal loops, or G-bulges, are, the least stable parts of the molecule. The G-bulges display high, conformational variability in the refined ensemble of structures, despite, the availability of many structural restraints for this region., Nevertheless, most conformations share a similar structural motif: a, guanine and an adenine from opposite strands form a GA mismatch stacked on, the top of the neighboring stem. The two remaining guanines are exposed, one in the minor groove and another in the major groove side of the helix, consistent with secondary structure probing data for SL1. These guanines, may be recognized by the nucleocapsid protein, which binds tightly to the, G-bulge in vitro.

About this Structure

2GM0 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.

Reference

NMR structure of the full-length linear dimer of stem-loop-1 RNA in the HIV-1 dimer initiation site., Ulyanov NB, Mujeeb A, Du Z, Tonelli M, Parslow TG, James TL, J Biol Chem. 2006 Jun 9;281(23):16168-77. Epub 2006 Apr 6. PMID:16603544

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