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Secondary Active Transport01:55

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Single-Molecule Imaging of Nuclear Transport
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Quantifying secondary transport at single-molecule resolution.

Gabriel A Fitzgerald1, Daniel S Terry1,2, Audrey L Warren3

  • 1Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.

Nature
|November 15, 2019
PubMed
Summary
This summary is machine-generated.

Researchers visualized individual secondary active transporters, MhsT, to understand their transport mechanisms. They discovered that transporter activity depends on orientation and substrate, revealing insights into neurotransmitter:sodium symporter function.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Biophysics

Background:

  • Secondary active transporters are crucial for physiological processes, utilizing ion gradients for membrane transport.
  • Investigating transporter mechanisms is challenging due to slow rates and ensemble method limitations.

Purpose of the Study:

  • To quantify the activity of individual MhsT transporters, a model for neurotransmitter:sodium symporters.
  • To elucidate the mechanism of substrate transport at the single-molecule level.

Main Methods:

  • Imaging individual MhsT transporter activity across lipid bilayers.
  • Quantifying transport at single- and multi-turnover resolution.
  • Analyzing substrate transport dynamics.

Main Results:

  • MhsT transporter activity is dependent on its physiological orientation.
  • The rate-limiting step in the transport cycle varies with the transported substrate.
  • Evidence suggests an extracellular allosteric binding site influences transport kinetics.

Conclusions:

  • Single-molecule imaging provides unprecedented resolution for studying transporter mechanisms.
  • MhsT's transport cycle is modulated by substrate binding and transporter orientation.
  • Findings offer insights into the functional dynamics of neurotransmitter:sodium symporters.