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

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 Syst

journal_title

Cell systems

authors

Mallam AL,Marcotte EM

doi

10.1016/j.cels.2017.04.006

subject

Has Abstract

pub_date

2017-05-24 00:00:00

pages

483-494

issue

5

eissn

2405-4712

issn

2405-4720

pii

S2405-4712(17)30138-2

journal_volume

4

pub_type

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