Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex
Summary: The endoplasmic reticulum (ER) membrane protein complex (EMC) is a key contributor to biogenesis and membrane integration of transmembrane proteins, but our understanding of its mechanisms and the range of EMC-dependent proteins remains incomplete. Here, we carried out an unbiased mass spec...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719310393 |
| _version_ | 1811202459630043136 |
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| author | Songhai Tian Quan Wu Bo Zhou Mei Yuk Choi Bo Ding Wei Yang Min Dong |
| author_facet | Songhai Tian Quan Wu Bo Zhou Mei Yuk Choi Bo Ding Wei Yang Min Dong |
| author_sort | Songhai Tian |
| collection | DOAJ |
| description | Summary: The endoplasmic reticulum (ER) membrane protein complex (EMC) is a key contributor to biogenesis and membrane integration of transmembrane proteins, but our understanding of its mechanisms and the range of EMC-dependent proteins remains incomplete. Here, we carried out an unbiased mass spectrometry (MS)-based quantitative proteomic analysis comparing membrane proteins in EMC-deficient cells to wild-type (WT) cells and identified 36 EMC-dependent membrane proteins and 171 EMC-independent membrane proteins. Of these, six EMC-dependent and six EMC-independent proteins were further independently validated. We found that a common feature among EMC-dependent proteins is that they contain transmembrane domains (TMDs) with polar and/or charged residues. Mutagenesis studies demonstrate that EMC dependency can be converted in cells by removing or introducing polar and/or charged residues within TMDs. Our studies expand the list of validated EMC-dependent and EMC-independent proteins and suggest that the EMC is involved in handling TMDs with residues challenging for membrane integration. : The endoplasmic reticulum membrane protein complex (EMC) contributes to the biogenesis of transmembrane proteins. Using mass spectrometry-based quantitative proteomic analysis, Tian et al. identify EMC-dependent and EMC-independent proteins. The authors find evidence that the EMC is involved in handling transmembrane domains with polar and/or charged residues that are challenging for membrane integration. Keywords: mass spectrometry-based proteomics, ER membrane protein complex, membrane protein synthesis, transmembrane domain, polar residue, charged residue, transporter activity, EMC, transmembrane domain, transporter, ion channels |
| first_indexed | 2024-04-12T02:39:05Z |
| format | Article |
| id | doaj.art-b5caf03056d64fdc8ec954551206fa9f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T02:39:05Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b5caf03056d64fdc8ec954551206fa9f2022-12-22T03:51:22ZengElsevierCell Reports2211-12472019-09-01281025172526.e5Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein ComplexSonghai Tian0Quan Wu1Bo Zhou2Mei Yuk Choi3Bo Ding4Wei Yang5Min Dong6Department of Urology, Boston Children’s Hospital, and Department of Surgery and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USADepartment of Urology, Boston Children’s Hospital, and Department of Surgery and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Central Laboratory of Medical Research Centre, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People’s Republic of ChinaDivision of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADivision of Genetics, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115, USABonacept LLC, San Diego, CA 92122, USADivision of Cancer Biology and Therapeutics, Departments of Surgery and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Urology, Boston Children’s Hospital, and Department of Surgery and Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Corresponding authorSummary: The endoplasmic reticulum (ER) membrane protein complex (EMC) is a key contributor to biogenesis and membrane integration of transmembrane proteins, but our understanding of its mechanisms and the range of EMC-dependent proteins remains incomplete. Here, we carried out an unbiased mass spectrometry (MS)-based quantitative proteomic analysis comparing membrane proteins in EMC-deficient cells to wild-type (WT) cells and identified 36 EMC-dependent membrane proteins and 171 EMC-independent membrane proteins. Of these, six EMC-dependent and six EMC-independent proteins were further independently validated. We found that a common feature among EMC-dependent proteins is that they contain transmembrane domains (TMDs) with polar and/or charged residues. Mutagenesis studies demonstrate that EMC dependency can be converted in cells by removing or introducing polar and/or charged residues within TMDs. Our studies expand the list of validated EMC-dependent and EMC-independent proteins and suggest that the EMC is involved in handling TMDs with residues challenging for membrane integration. : The endoplasmic reticulum membrane protein complex (EMC) contributes to the biogenesis of transmembrane proteins. Using mass spectrometry-based quantitative proteomic analysis, Tian et al. identify EMC-dependent and EMC-independent proteins. The authors find evidence that the EMC is involved in handling transmembrane domains with polar and/or charged residues that are challenging for membrane integration. Keywords: mass spectrometry-based proteomics, ER membrane protein complex, membrane protein synthesis, transmembrane domain, polar residue, charged residue, transporter activity, EMC, transmembrane domain, transporter, ion channelshttp://www.sciencedirect.com/science/article/pii/S2211124719310393 |
| spellingShingle | Songhai Tian Quan Wu Bo Zhou Mei Yuk Choi Bo Ding Wei Yang Min Dong Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex Cell Reports |
| title | Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex |
| title_full | Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex |
| title_fullStr | Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex |
| title_full_unstemmed | Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex |
| title_short | Proteomic Analysis Identifies Membrane Proteins Dependent on the ER Membrane Protein Complex |
| title_sort | proteomic analysis identifies membrane proteins dependent on the er membrane protein complex |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719310393 |
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