title: 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 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.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ori
authors.forename: Niccolò
authors.initials: N
authors.lastname: Banterle
authors.forename: Murat
authors.initials: M
authors.lastname: Iskar
authors.forename: Amparo
authors.initials: A
authors.lastname: Andrés-Pons
authors.forename: Claudia
authors.initials: C
authors.lastname: Escher
authors.forename: Huy
authors.initials: H
authors.lastname: Khanh Bui
authors.forename: Lenore
authors.initials: L
authors.lastname: Sparks
authors.forename: Victor
authors.initials: V
authors.lastname: Solis-Mezarino
authors.forename: Oliver
authors.initials: O
authors.lastname: Rinner
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Edward A
authors.initials: EA
authors.lastname: Lemke
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
mesh_terms: D002138:Calibration; D002460:Cell Line; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008853:Microscopy / Q000379:methods; D022022:Nuclear Pore / Q000737:chemistry* / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D028861:Nuclear Pore Complex Proteins