TY  - INPR
A1  - Mosalaganti, Shyamal Narayan
A1  - Obarska-Kosinska, Agnieszka
A1  - Siggel, Marc
A1  - Turoňová, Beata
A1  - Zimmerli, Christian Eugen
A1  - Buczak, Katarzyna
A1  - Schmidt, Florian H.
A1  - Margiotta, Erica
A1  - Mackmull, Marie-Therese
A1  - Hagen, Wim
A1  - Hummer, Gerhard
A1  - Beck, Martin
A1  - Kosinski, Jan
T1  - Artificial intelligence reveals nuclear pore complexity
T2  - bioRxiv
N2  - Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport. Their intricate 120 MDa architecture remains incompletely understood. Here, we report a near-complete structural model of the human NPC scaffold with explicit membrane and in multiple conformational states. We combined AI-based structure prediction with in situ and in cellulo cryo-electron tomography and integrative modeling. We show that linker Nups spatially organize the scaffold within and across subcomplexes to establish the higher-order structure. Microsecond-long molecular dynamics simulations suggest that the scaffold is not required to stabilize the inner and outer nuclear membrane fusion, but rather widens the central pore. Our work exemplifies how AI-based modeling can be integrated with in situ structural biology to understand subcellular architecture across spatial organization levels.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72959
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-729597
IS  - 2021.10.26.465776
ER  -