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TitleThe cellular environment shapes the nuclear pore complex architecture.
Journal, issue, pagesNature, Vol. 598, Issue 7882, Page 667-671, Year 2021
Publish dateOct 13, 2021
AuthorsAnthony P Schuller / Matthias Wojtynek / David Mankus / Meltem Tatli / Rafael Kronenberg-Tenga / Saroj G Regmi / Phat V Dip / Abigail K R Lytton-Jean / Edward J Brignole / Mary Dasso / Karsten Weis / Ohad Medalia / Thomas U Schwartz /
PubMed AbstractNuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE). These multi-megadalton structures are composed of about ...Nuclear pore complexes (NPCs) create large conduits for cargo transport between the nucleus and cytoplasm across the nuclear envelope (NE). These multi-megadalton structures are composed of about thirty different nucleoporins that are distributed in three main substructures (the inner, cytoplasmic and nucleoplasmic rings) around the central transport channel. Here we use cryo-electron tomography on DLD-1 cells that were prepared using cryo-focused-ion-beam milling to generate a structural model for the human NPC in its native environment. We show that-compared with previous human NPC models obtained from purified NEs-the inner ring in our model is substantially wider; the volume of the central channel is increased by 75% and the nucleoplasmic and cytoplasmic rings are reorganized. Moreover, the NPC membrane exhibits asymmetry around the inner-ring complex. Using targeted degradation of Nup96, a scaffold nucleoporin of the cytoplasmic and nucleoplasmic rings, we observe the interdependence of each ring in modulating the central channel and maintaining membrane asymmetry. Our findings highlight the inherent flexibility of the NPC and suggest that the cellular environment has a considerable influence on NPC dimensions and architecture.
External linksNature / PubMed:34646014 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution33 - 39 Å
Structure data

EMDB-12811:
Segment of the cytoplasmic ring of the human nuclear pore complex
Method: EM (subtomogram averaging) / Resolution: 33 Å

EMDB-12812:
Segment of the inner ring of the human nuclear pore complex
Method: EM (subtomogram averaging) / Resolution: 38 Å

EMDB-12813:
Segment of the nucleoplasmic ring of the human nuclear pore complex
Method: EM (subtomogram averaging) / Resolution: 39 Å

EMDB-12814: In-cell human nuclear pore complex
PDB-7peq: Model of the outer rings of the human nuclear pore complex
PDB-7per: Model of the inner ring of the human nuclear pore complex
Method: EM (subtomogram averaging) / Resolution: 35 Å

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / Nuclear Pore Complex / NPC

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