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Extracellular Juxtamembrane Segment of ADAM17 Interacts with Membranes and Is Essential for Its Shedding Activity

Stefan Düsterhöft, Matthias Michalek, Felix Kordowski1

  • 1Department of Dermatology and Allergology, University Hospital Schleswig-Holstein , Campus Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany.

Biochemistry
|September 9, 2015
PubMed

Insights

The Conserved ADAM-seventeeN Dynamic Interaction Sequence (CANDIS) in ADAM17 interacts with lipid bilayers. This interaction may regulate the shedding activity of ADAM17, impacting biological processes like inflammation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Protein shedding regulates key biological processes like cell differentiation, regeneration, and cancer progression.
  • A Disintegrin And Metalloprotease-17 (ADAM17) is a major sheddase enzyme involved in these processes.
  • ADAM17 substrates include crucial inflammatory mediators such as interleukin-6 receptor (IL-6R) and tumor necrosis factor (TNF-α).

Purpose of the Study:

  • To investigate the role of the Conserved ADAM-seventeeN Dynamic Interaction Sequence (CANDIS) in ADAM17 function.
  • To determine if CANDIS interacts with lipid bilayers and how this might influence ADAM17 activity.

Main Methods:

  • In vitro lipid bilayer interaction assays were performed using the CANDIS segment.
  • Analysis of ADAM17 substrate shedding in relation to CANDIS properties.

Main Results:

  • The CANDIS segment demonstrated the ability to interact with lipid bilayers in vitro.
  • This interaction suggests a novel mechanism for regulating ADAM17 shedding activity.

Conclusions:

  • CANDIS plays a dual role in ADAM17 function, participating in both substrate recognition and membrane interaction.
  • The lipid-binding property of CANDIS may be a key factor in modulating ADAM17's enzymatic activity and its role in biological regulation.

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