Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines
Abstract To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super‐resolution microscopy approach to determine the absolute stoichiometry of the human nuclear p...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2013-03-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2013.4 |
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| _version_ | 1849739633673371648 |
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| author | Alessandro Ori Niccolò Banterle Murat Iskar Amparo Andrés‐Pons Claudia Escher Huy Khanh Bui Lenore Sparks Victor Solis‐Mezarino Oliver Rinner Peer Bork Edward A Lemke Martin Beck |
| author_facet | Alessandro Ori Niccolò Banterle Murat Iskar Amparo Andrés‐Pons Claudia Escher Huy Khanh Bui Lenore Sparks Victor Solis‐Mezarino Oliver Rinner Peer Bork Edward A Lemke Martin Beck |
| author_sort | Alessandro Ori |
| collection | DOAJ |
| description | Abstract To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super‐resolution microscopy approach to determine the absolute stoichiometry of the human nuclear pore complex (NPC), possibly the largest eukaryotic protein complex. We show that the human NPC has a previously unanticipated stoichiometry that varies across cancer cell types, tissues and in disease. Using large‐scale proteomics, we provide evidence that more than one third of the known, well‐defined nuclear protein complexes display a similar cell type‐specific variation of their subunit stoichiometry. Our data point to compositional rearrangement as a widespread mechanism for adapting the functions of molecular machines toward cell type‐specific constraints and context‐dependent needs, and highlight the need of deeper investigation of such structural variants. |
| format | Article |
| id | doaj-art-d19969a76d3b45278d9f800f429e461a |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2013-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-d19969a76d3b45278d9f800f429e461a2025-08-20T03:06:13ZengSpringer NatureMolecular Systems Biology1744-42922013-03-019111110.1038/msb.2013.4Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machinesAlessandro Ori0Niccolò Banterle1Murat Iskar2Amparo Andrés‐Pons3Claudia Escher4Huy Khanh Bui5Lenore Sparks6Victor Solis‐Mezarino7Oliver Rinner8Peer Bork9Edward A Lemke10Martin Beck11Structural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryBiognosys AGStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryBiognosys AGStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryStructural and Computational Biology Unit, European Molecular Biology LaboratoryAbstract To understand the structure and function of large molecular machines, accurate knowledge of their stoichiometry is essential. In this study, we developed an integrated targeted proteomics and super‐resolution microscopy approach to determine the absolute stoichiometry of the human nuclear pore complex (NPC), possibly the largest eukaryotic protein complex. We show that the human NPC has a previously unanticipated stoichiometry that varies across cancer cell types, tissues and in disease. Using large‐scale proteomics, we provide evidence that more than one third of the known, well‐defined nuclear protein complexes display a similar cell type‐specific variation of their subunit stoichiometry. Our data point to compositional rearrangement as a widespread mechanism for adapting the functions of molecular machines toward cell type‐specific constraints and context‐dependent needs, and highlight the need of deeper investigation of such structural variants.https://doi.org/10.1038/msb.2013.4fluorophore countingnucleoporinprotein complex‐based analysissuper‐resolution microscopytargeted proteomics |
| spellingShingle | Alessandro Ori Niccolò Banterle Murat Iskar Amparo Andrés‐Pons Claudia Escher Huy Khanh Bui Lenore Sparks Victor Solis‐Mezarino Oliver Rinner Peer Bork Edward A Lemke Martin Beck Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines Molecular Systems Biology fluorophore counting nucleoporin protein complex‐based analysis super‐resolution microscopy targeted proteomics |
| title | Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines |
| title_full | Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines |
| title_fullStr | Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines |
| title_full_unstemmed | Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines |
| title_short | Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines |
| title_sort | cell type specific nuclear pores a case in point for context dependent stoichiometry of molecular machines |
| topic | fluorophore counting nucleoporin protein complex‐based analysis super‐resolution microscopy targeted proteomics |
| url | https://doi.org/10.1038/msb.2013.4 |
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