Proteomics

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Direct visualization of ERAD nanocompartments within the cell

ABSTRACT: ER-associated degradation (ERAD) is an evolutionarily-conserved quality control mechanism where misfolded proteins are removed from the endoplasmic reticulum (ER) and degraded by the ubiquitin-proteasome system. While many ERAD-mediating proteins have been identified, it is unknown how they are spatially organized within the cell. Using in situ cryo-electron tomography to image the native molecular landscape of Chlamydomonas, we discovered that ERAD proteins are concentrated within ~200 nm cytosolic foci that contact the ER membrane away from the ER-Golgi interface. These ribosome-excluding ERAD nanocompartments consist of a core of clustered proteasomes surrounded by Cdc48. Active proteasomes directly engage with the ER membrane, indicating an additional Cdc48-independent mechanism for extraction of misfolded proteins. Our study reveals that ERAD has precise cellular architecture, which likely enables efficient protein quality control.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Chlamydomonas Reinhardtii

SUBMITTER: Nagarjuna Nagaraj  

LAB HEAD: Wolfgang Baumeister

PROVIDER: PXD009375 | Pride | 2020-05-26

REPOSITORIES: Pride

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Direct visualization of degradation microcompartments at the ER membrane.

Albert Sahradha S   Wietrzynski Wojciech W   Lee Chia-Wei CW   Schaffer Miroslava M   Beck Florian F   Schuller Jan M JM   Salomé Patrice A PA   Plitzko Jürgen M JM   Baumeister Wolfgang W   Engel Benjamin D BD  

Proceedings of the National Academy of Sciences of the United States of America 20191227 2

To promote the biochemical reactions of life, cells can compartmentalize molecular interaction partners together within separated non-membrane-bound regions. It is unknown whether this strategy is used to facilitate protein degradation at specific locations within the cell. Leveraging in situ cryo-electron tomography to image the native molecular landscape of the unicellular alga <i>Chlamydomonas reinhardtii</i>, we discovered that the cytosolic protein degradation machinery is concentrated with  ...[more]

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