Cell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines

Molecular Systems Biology

Alessandro Ori¹  Niccolò Banterle¹  Murat Iskar¹  Amparo Andrés-Pons¹  Claudia Escher²  Huy Khanh Bui¹  Lenore Sparks¹  Victor Solis-Mezarino¹  Oliver Rinner²  Peer Bork¹  Edward A Lemke¹ 

[1] Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany;Biognosys AG, Schlieren, Switzerland

关键词: fluorophore counting;    nucleoporin;    protein complex‐based analysis;    super‐resolution microscopy;    targeted proteomics;   

DOI  :  10.1038/msb.2013.4

来源: Wiley

【 摘 要 】

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.

Synopsis

The stoichiometry of the human nuclear pore complex is revealed by targeted mass spectrometry and super-resolution microscopy. The analysis reveals that the composition of the nuclear pore and other nuclear protein complexes is remodeled as a function of the cell type.

• The human NPC has a previously unanticipated stoichiometry that varies across cell types.
• Primarily functional Nups are dynamic, while the NPC scaffold is static.
• Stoichiometries of many complexes are fine-tuned toward cell type-specific needs.

【 授权许可】

CC BY-NC-SA   
Copyright © 2013 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.