研究人员报告了一个具有明确的膜和多种构象状态的人类核孔复合体（NPC）支架的70兆道尔顿模型。研究人员将基于人工智能（AI）的结构预测与原位和细胞低温电子断层扫描以及综合建模相结合。结果表明，连接核蛋白在空间上将支架组织在子复合物内部和之间，进而建立高阶结构。长达微秒的分子动力学模拟表明，支架不需要稳定内外核膜的融合，而是扩大中心孔。这些工作体现了基于人工智能的建模如何与原位结构生物学相结合，进而了解跨空间组织水平的亚细胞结构。
据介绍，NPC介导核细胞质的运输。它们复杂的120兆道尔顿结构仍未被完全理解。
附：英文原文
Title: AI-based structure prediction empowers integrative structural analysis of human nuclear pores
Author: Shyamal Mosalaganti, Agnieszka Obarska-Kosinska, Marc Siggel, Reiya Taniguchi, Beata Turoňová, Christian E. Zimmerli, Katarzyna Buczak, Florian H. Schmidt, Erica Margiotta, Marie-Therese Mackmull, Wim J. H. Hagen, Gerhard Hummer, Jan Kosinski, Martin Beck
Issue&Volume: 2022-06-10
Abstract: Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport. Their intricate 120-megadalton architecture remains incompletely understood. Here, we report a 70-megadalton model of the human NPC scaffold with explicit membrane and in multiple conformational states. We combined artificial intelligence (AI)–based structure prediction with in situ and in cellulo cryo–electron tomography and integrative modeling. We show that linker nucleoporins 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.
DOI: abm9506
Source: https://www.science.org/doi/10.1126/science.abm9506