Abstract:
:Recent mass spectrometry maps of the human interactome independently support the existence of a large multiprotein complex, dubbed "Commander." Broadly conserved across animals and ubiquitously expressed in nearly every human cell type examined thus far, Commander likely plays a fundamental cellular function, akin to other ubiquitous machines involved in expression, proteostasis, and trafficking. Experiments on individual subunits support roles in endosomal protein sorting, including the trafficking of Notch proteins, copper transporters, and lipoprotein receptors. Commander is critical for vertebrate embryogenesis, and defects in the complex and its interaction partners disrupt craniofacial, brain, and heart development. Here, we review the synergy between large-scale proteomic efforts and focused studies in the discovery of Commander, describe its composition, structure, and function, and discuss how it illustrates the power of systems biology. Based on 3D modeling and biochemical data, we draw strong parallels between Commander and the retromer cargo-recognition complex, laying a foundation for future research into Commander's role in human developmental disorders.
journal_name
Cell Systjournal_title
Cell systemsauthors
Mallam AL,Marcotte EMdoi
10.1016/j.cels.2017.04.006subject
Has Abstractpub_date
2017-05-24 00:00:00pages
483-494issue
5eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30138-2journal_volume
4pub_type
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