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Updated: Jun 4, 2025

Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
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Human transporter de-oligomerization regulates copper uptake into cells.

Tai-Yen Chen1, Meng-Hsuan Wen1, Huanhuan Chen1

  • 1University of Houston.

Research Square
|December 23, 2024
PubMed
Summary

Excess copper causes the CTR1 transporter to break apart into single units, rapidly stopping copper uptake and preventing cell damage. This structural change is key to maintaining copper balance.

Keywords:
CTR1OligomerizationRab5copper transportendocytosissingle-molecule localization microscopysingle-molecule neighbor density analysis

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Copper is vital for cellular functions like energy production and antioxidant defense.
  • Dysregulated copper levels can cause toxicity and disease.
  • Copper Transporter 1 (CTR1) is crucial for cellular copper uptake and homeostasis.

Purpose of the Study:

  • To investigate the mechanism of rapid regulation of cellular copper uptake by CTR1.
  • To understand how CTR1 responds to excess copper levels.

Main Methods:

  • Single-molecule localization microscopy (SMLM) was employed to visualize CTR1 dynamics.
  • Single-molecule neighbor density assays were used to quantify CTR1 clustering and monomerization.
  • An endocytosis-deficient CTR1 mutant (M150L) was utilized for comparison.

Main Results:

  • Excess copper induces the dissociation of trimeric CTR1 into monomers.
  • This monomerization event precedes CTR1 endocytosis.
  • The endocytosis-deficient CTR1 (M150L) mutant showed a blockage in copper-induced monomerization.
  • CTR1 monomerization was identified as a rapid mechanism to halt copper uptake.

Conclusions:

  • Protein oligomerization state changes represent a novel regulatory mechanism for metal transporters.
  • CTR1 structural changes (trimer to monomer) are directly linked to its endocytosis and cellular copper homeostasis.
  • This study provides new insights into preventing copper overload at the cellular level.