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Anomalous diffusion reports on the interaction of misfolded proteins with the quality control machinery in the

Nina Malchus1, Matthias Weiss

  • 1Cellular Biophysics Group, German Cancer Research Center, c/o BIOQUANT, Heidelberg, Germany.

Biophysical Journal
|August 18, 2010
PubMed

Insights

Unfolded proteins in the endoplasmic reticulum (ER) interact with quality control machinery. Chaperone calnexin prevents ER poisoning by dissolving protein oligomers, promoting protein mobility.

Area of Science:

  • Cell Biology
  • Biophysics

Background:

  • Transmembrane proteins enter the endoplasmic reticulum (ER) as unfolded chains.
  • These proteins interact with the ER's quality control machinery during folding.

Purpose of the Study:

  • To investigate the in vivo interactions of unfolded transmembrane proteins with ER quality control machinery.
  • To understand the role of chaperones in protein folding and ER homeostasis.

Main Methods:

  • Utilized fluorescence correlation spectroscopy (FCS) to study the diffusion of VSVG ts045 protein in vivo.
  • Employed computational simulations to complement experimental data.

Main Results:

  • Both folded and unfolded VSVG ts045 exhibited anomalous diffusion.
  • Unfolded VSVG ts045 showed significantly more anomalous diffusion, suggesting obstruction.
  • Complex formation with calnexin or using a single-glycan mutant reduced this anomalous diffusion.

Conclusions:

  • The ER quality control sensor (UGT1) oligomerizes unfolded VSVG ts045, causing obstructed diffusion.
  • Calnexin disassembles these oligomers, increasing protein mobility and preventing ER dysfunction.

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