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A novel motif identified in dependence receptors

Gabriel del Rio1, Darci J Kane, Keith D Ball

  • 1Buck Institute for Age Research, Novato, California, United States of America.

Plos One
|May 24, 2007
PubMed

Insights

Researchers identified a novel transmembrane motif, the dependence-associated receptor transmembrane (DART) motif, common to all dependence receptors. This discovery aids in understanding programmed cell death signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Programmed cell death signaling is crucial in development, cellular turnover, and diseases like cancer and neurodegeneration.
  • Signaling occurs via death receptors or dependence receptors, but dependence receptors lack identified common structural domains.
  • Understanding dependence receptor structure is key to elucidating their roles in cell signaling.

Purpose of the Study:

  • To identify a common structural domain among dependence receptors.
  • To characterize the novel identified motif and its prevalence in human transmembrane proteins.
  • To explore potential functions of the novel motif.

Main Methods:

  • Utilized Multiple Expectation Maximization for Motif Elicitation (MEME) and Motif Alignment and Search Tool (MAST) software.
  • Analyzed 3,465 human transmembrane proteins for the presence of the novel motif.
  • Predicted secondary structure and investigated potential protein processing pathways.

Main Results:

  • Identified a novel transmembrane motif, the dependence-associated receptor transmembrane (DART) motif, common to all described dependence receptors.
  • The DART motif was found in 25 out of 3,465 (0.7%) human transmembrane proteins.
  • The motif exhibits an alpha-helical structure with a high valine content, and at least four associated proteins undergo regulated intramembrane proteolysis.

Conclusions:

  • The DART motif represents a shared structural feature of dependence receptors, previously unidentified.
  • The motif's prevalence and structural characteristics suggest a significant role in transmembrane protein function.
  • Further research is needed to determine the precise function of the DART motif in protein processing, interactions, or homomultimerization.

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