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MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction

Long Fan1, Li Liu2, Cuicui Zhu3

  • 1Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. fl891116@163.com.

International Journal of Molecular Sciences
|May 31, 2016
PubMed

Insights

Membrane type-1 matrix metalloproteinase (MT1-MMP) inhibits bone marrow stromal cell antigen 2 (Bst-2) tetherin activity. This interaction, involving specific protein domains, leads to the downregulation of both Bst-2 and MT1-MMP.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Bone marrow stromal cell antigen 2 (Bst-2) is a type II membrane protein functioning as a tetherin to restrict virion release from infected cells.
  • Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease crucial for cell growth and migration, notably by activating proMMP-2 to MMP2.

Purpose of the Study:

  • To investigate the inhibitory effect of MT1-MMP on Bst-2 tetherin activity.
  • To elucidate the molecular mechanisms and specific domains involved in the interaction between Bst-2 and MT1-MMP.

Main Methods:

  • Virion release assays
  • Co-immunoprecipitation assays
  • Immunostaining and Confocal Microscopy
  • Mutant experiments

Main Results:

  • MT1-MMP was demonstrated to inhibit Bst-2 tetherin activity through direct interaction.
  • The cytoplasmic domains of Bst-2 and MT1-MMP, specifically the N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP, are critical for this interaction.
  • MT1-MMP and Bst-2 form granular particles that traffic into the cytoplasm, leading to the inhibition of both proteins.
  • Mutant experiments revealed the N-terminal domain of Bst-2 is also important for inhibiting the MT1-MMP/proMMP2/MMP2 pathway.

Conclusions:

  • MT1-MMP acts as a novel inhibitor of Bst-2 in cells expressing MT1-MMP.
  • The N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP are crucial for the downregulation of Bst-2 activity by MT1-MMP.
Keywords:
Membrane type-1 matrix metalloproteinase (MT1-MMP)bone marrow stromal cell antigen 2 (Bst-2)tetherinvirus release

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