Molecular architecture of the inner ring scaffold of the human nuclear pore complex

• Published in: Science (American Association for the Advancement of Science) Vol. 352; no. 6283; pp. 363 - 365
• Main Authors: Kosinski, Jan, Mosalaganti, Shyamal, von Appen, Alexander, Teimer, Roman, DiGuilio, Amanda L., Wan, William, Bui, Khanh Huy, Hagen, Wim J.H., Briggs, John A. G., Glavy, Joseph S., Hurt, Ed, Beck, Martin
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 15.04.2016; The American Association for the Advancement of Science
• Subjects: Active Transport, Cell Nucleus; Cryoelectron Microscopy; Crystallography; Cytoplasm; Electron Microscope Tomography; HeLa Cells; Humans; Mass Spectrometry; Models, Molecular; Nuclear Matrix - metabolism; Nuclear Matrix - ultrastructure; Nuclear medicine; Nuclear Pore - metabolism; Nuclear Pore - ultrastructure; Nuclear Pore Complex Proteins - chemistry; Nuclear Pore Complex Proteins - genetics; Nuclear Pore Complex Proteins - metabolism; Scientific Concepts; Tomography
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aaf0643

Nuclear pore complexes (NPCs) are 110-megadalton assemblies that mediate nucleocytoplasmic transport. NPCs are built from multiple copies of ~30 different nucleoporins, and understanding how these nucleoporins assemble into the NPC scaffold imposes a formidable challenge. Recently, it has been shown how the Y complex, a prominent NPC module, forms the outer rings of the nuclear pore. However, the organization of the inner ring has remained unknown until now. We used molecular modeling combined with cross-linking mass spectrometry and cryo-electron tomography to obtain a composite structure of the inner ring. This architectural map explains the vast majority of the electron density of the scaffold. We conclude that despite obvious differences in morphology and composition, the higher-order structure of the inner and outer rings is unexpectedly similar.