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Related Experiment Video

Updated: May 2, 2026

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
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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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Microsecond dynamics control the HIV-1 Envelope conformation.

Ashley L Bennett1, Robert Edwards1, Irina Kosheleva2

  • 1Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.

Science Advances
|February 2, 2024
PubMed
Summary
This summary is machine-generated.

Researchers studied HIV-1 Envelope glycoprotein dynamics using time-resolved X-ray scattering. They uncovered microsecond timescale transitions crucial for controlling its structure and impacting HIV vaccine design.

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Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
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Area of Science:

  • Structural biology
  • Virology
  • Biophysics

Background:

  • The HIV-1 Envelope (Env) glycoprotein drives viral entry via complex structural changes.
  • Understanding Env dynamics is key to developing effective HIV vaccines.
  • Previous studies lacked experimental data on microsecond timescale Env dynamics.

Purpose of the Study:

  • To investigate the microsecond timescale dynamics of the HIV-1 Env glycoprotein.
  • To identify novel structural transitions and their functional relevance.
  • To inform the design of improved HIV Env-based vaccines.

Main Methods:

  • Time-resolved, temperature-jump small-angle X-ray scattering (TR-T-jump SAXS).
  • Analysis of HIV-1 Env SOSIP ectodomain constructs.
  • Engineering of disulfide-stabilized Env constructs.

Main Results:

  • Observed microsecond timescale structural rearrangements in Env variants.
  • Identified a known transition with a time constant in the hundreds of microseconds.
  • Discovered a novel order-to-disorder transition at the trimer apex below 10 μs.
  • Engineered a stabilized Env SOSIP construct in the prefusion closed state.

Conclusions:

  • Microsecond dynamics are critical for controlling HIV Env conformation.
  • These dynamics have significant implications for HIV vaccine development.
  • Stabilizing the prefusion closed state is a viable strategy for vaccine design.