The ER membrane protein complex is a transmembrane domain insertase
Insertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here, we found that known membrane insertion pathways fail to effectively engage...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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American Association for the Advancement of Science
2017
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| _version_ | 1797060276728627200 |
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| author | Guna, A Volkmar, N Christianson, J Hegde, R |
| author_facet | Guna, A Volkmar, N Christianson, J Hegde, R |
| author_sort | Guna, A |
| collection | OXFORD |
| description | Insertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here, we found that known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells. Purified EMC in synthetic liposomes catalyzed insertion of its substrates in a reconstituted system. Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms. |
| first_indexed | 2024-03-06T20:14:56Z |
| format | Journal article |
| id | oxford-uuid:2bcec143-5734-4b07-acc2-819b2fda3323 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:14:56Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:2bcec143-5734-4b07-acc2-819b2fda33232022-03-26T12:33:21ZThe ER membrane protein complex is a transmembrane domain insertaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2bcec143-5734-4b07-acc2-819b2fda3323EnglishSymplectic Elements at OxfordAmerican Association for the Advancement of Science2017Guna, AVolkmar, NChristianson, JHegde, RInsertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here, we found that known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells. Purified EMC in synthetic liposomes catalyzed insertion of its substrates in a reconstituted system. Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms. |
| spellingShingle | Guna, A Volkmar, N Christianson, J Hegde, R The ER membrane protein complex is a transmembrane domain insertase |
| title | The ER membrane protein complex is a transmembrane domain insertase |
| title_full | The ER membrane protein complex is a transmembrane domain insertase |
| title_fullStr | The ER membrane protein complex is a transmembrane domain insertase |
| title_full_unstemmed | The ER membrane protein complex is a transmembrane domain insertase |
| title_short | The ER membrane protein complex is a transmembrane domain insertase |
| title_sort | er membrane protein complex is a transmembrane domain insertase |
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