Open AccessCell type‐specific nuclear pores: a case in point for context‐dependent stoichiometry of molecular machines
Author(s) -
Ori Alessandro,
Banterle Niccolò,
Iskar Murat,
AndrésPons Amparo,
Escher Claudia,
Khanh Bui Huy,
Sparks Lenore,
SolisMezarino Victor,
Rinner Oliver,
Bork Peer,
Lemke Edward A,
Beck Martin
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2013.4
Subject(s) - biology , context (archaeology) , proteomics , computational biology , protein subunit , stoichiometry , nuclear pore , cell type , function (biology) , cell , biochemistry , microbiology and biotechnology , nucleus , chemistry , gene , paleontology , organic chemistry
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.