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Related Experiment Video

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Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
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A proposal for a new HIV-1 DLS structural model.

Jun-ichi Sakuragi1, Hirotaka Ode, Sayuri Sakuragi

  • 1Department of Viral Infections, RIMD, Osaka Univ. 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan. sakuragi@biken.osaka-u.ac.jp

Nucleic Acids Research
|February 14, 2012
PubMed
Summary

Researchers mapped the human immunodeficiency virus type 1 (HIV-1) dimer linkage sequence (DLS), revealing a novel pseudoknot-like structure. This stable conformation may be key to the viral life cycle and a potential therapeutic target.

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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

Published on: September 15, 2010

Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • The dimer initiation site/dimer linkage sequence (DIS/DLS) is crucial for the human immunodeficiency virus type 1 (HIV-1) RNA genome.
  • This region plays essential roles throughout the viral life cycle.

Purpose of the Study:

  • To perform detailed mapping of functional base pairs within the HIV-1 DLS.
  • To propose new 3D models of the HIV-1 DLS based on experimental findings.

Main Methods:

  • Utilized a novel assay to map the necessary and sufficient region for RNA dimerization in HIV-1 virions.
  • Performed detailed functional base-pairing analysis within the HIV-1 DLS.

Main Results:

  • Identified a previously unobserved stem formation between distant regions within the DLS.
  • Revealed a unique pseudoknot-like conformation in the HIV-1 DLS structure.
  • The proposed pseudoknot-like structure is thermodynamically stable and sterically restricts conformational diversity.

Conclusions:

  • The novel pseudoknot-like conformation of the HIV-1 DLS is a foundational structural element.
  • This unique structure likely contributes to the viral life cycle.
  • The DLS pseudoknot represents a potential novel target for anti-HIV-1 therapies.