The Structure of the Nuclear Pore Complex (An Update)

Annu Rev Biochem. 2019 Jun 20;88:725-783. doi: 10.1146/annurev-biochem-062917-011901. Epub 2019 Mar 18.

Abstract

The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein subunits, ∼110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures, combined with biochemical reconstitution experiments, cross-linking mass spectrometry, and cryo-electron tomography, has facilitated the determination of the near-atomic overall architecture of the symmetric core of the human, fungal, and algal NPCs. Here, we discuss the insights gained from these new advances and outstanding issues regarding NPC structure and function. The powerful combination of bottom-up and top-down approaches toward determining the structure of the NPC offers a paradigm for uncovering the architectures of other complex biological machines to near-atomic resolution.

Keywords: X-ray crystallography; electron microscopy; integrative structural biology; mRNA export; nuclear pore complex; nucleocytoplasmic transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Nucleus / metabolism
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Eukaryota / metabolism
  • Eukaryota / ultrastructure
  • Humans
  • Models, Molecular*
  • Nuclear Pore / metabolism*
  • Nuclear Pore / ultrastructure
  • Nuclear Pore Complex Proteins / chemistry
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Conformation
  • Protein Subunits
  • RNA, Messenger / metabolism

Substances

  • Nuclear Pore Complex Proteins
  • Protein Subunits
  • RNA, Messenger