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Systems-wide Studies Uncover Commander, a Multiprotein Complex Essential to Human Development.

Anna L Mallam1, Edward M Marcotte1

  • 1Department of Molecular Biosciences, Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.

Cell Systems
|May 26, 2017
PubMed
Summary
This summary is machine-generated.

Commander, a newly discovered multiprotein complex, is vital for fundamental cellular functions and vertebrate development. Its disruption impacts craniofacial, brain, and heart formation, suggesting roles in developmental disorders.

Keywords:
Commander complexdevelopmental disordersendosomal protein sortingmammalian interactomemultiprotein complexsystem-wide studies

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Area of Science:

  • Cell Biology
  • Proteomics
  • Developmental Biology

Background:

  • Mass spectrometry has revealed a large multiprotein complex, named Commander, conserved across animals and ubiquitously expressed in human cells.
  • Commander is hypothesized to perform fundamental cellular functions, similar to other major cellular machinery involved in gene expression, protein homeostasis, and trafficking.

Purpose of the Study:

  • To review the discovery, composition, structure, and function of the Commander complex.
  • To explore the synergy between large-scale proteomics and focused studies in identifying Commander.
  • To establish parallels between Commander and the retromer complex for future research directions.

Main Methods:

  • Utilized mass spectrometry to map the human interactome and identify Commander.
  • Conducted experiments on individual subunits to elucidate functional roles.
  • Employed 3D modeling and biochemical data to analyze complex structure and compare it to known complexes.

Main Results:

  • Commander is a broadly conserved, ubiquitously expressed multiprotein complex.
  • Subunit studies indicate roles in endosomal protein sorting, including trafficking of Notch proteins, copper transporters, and lipoprotein receptors.
  • Commander is essential for vertebrate embryogenesis; defects cause craniofacial, brain, and heart developmental disruptions.

Conclusions:

  • Commander plays a fundamental role in cellular processes and vertebrate development.
  • The discovery of Commander highlights the power of systems biology approaches.
  • Commander shares structural and functional similarities with the retromer complex, providing a basis for investigating its role in human developmental disorders.