Determining the architectures of macromolecular assemblies

Frank Alber, Svetlana Dokudovskaya, Liesbeth M. Veenhoff, Wenzhu Zhang, Julia Kipper, Damien Devos, Adisetyantari Suprapto, Orit Karni-Schmidt, Rosemary Williams, Brian T. Chait, Michael P. Rout, Andrej Sali*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

406 Citations (Scopus)
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Abstract

To understand the workings of a living cell, we need to know the architectures of its macromolecular assemblies. Here we show how proteomic data can be used to determine such structures. The process involves the collection of sufficient and diverse high-quality data, translation of these data into spatial restraints, and an optimization that uses the restraints to generate an ensemble of structures consistent with the data. Analysis of the ensemble produces a detailed architectural map of the assembly. We developed our approach on a challenging model system, the nuclear pore complex (NPC). The NPC acts as a dynamic barrier, controlling access to and from the nucleus, and in yeast is a 50 MDa assembly of 456 proteins. The resulting structure, presented in an accompanying paper, reveals the configuration of the proteins in the NPC, providing insights into its evolution and architectural principles. The present approach should be applicable to many other macromolecular assemblies.

Original languageEnglish
Pages (from-to)683-694
Number of pages12
JournalNature
Volume450
Issue number7170
DOIs
Publication statusPublished - 29-Nov-2007

Keywords

  • NUCLEAR-PORE COMPLEX
  • NUCLEOCYTOPLASMIC TRANSPORT
  • CRYOELECTRON TOMOGRAPHY
  • PROTEIN INTERACTIONS
  • NUCLEOPORINS
  • IDENTIFICATION
  • SACCHAROMYCES
  • PREDICTION
  • SUBUNIT
  • ALPHA

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