Multiple conformational switches in a GTPase complex control co-translational protein targeting

Xin Zhang, Christiane Schaffitzel, Nenad Ban, Shu-ou Shan

Research output: Contribution to journalArticle (Academic Journal)peer-review

90 Citations (Scopus)

Abstract

The "GTPase switch" paradigm, in which a GTPase switches between an active, GTP-bound state and an inactive, GDP-bound state through the recruitment of nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs), has been used to interpret the regulatory mechanism of many GTPases. A notable exception to this paradigm is provided by two GTPases in the signal recognition particle (SRP) and the SRP receptor (SR) that control the co-translational targeting of proteins to cellular membranes. Instead of the classical "GTPase switch," both the SRP and SR undergo a series of discrete conformational rearrangements during their interaction with one another, culminating in their reciprocal GTPase activation. Here, we show that this series of rearrangements during SRP-SR binding and activation provide important control points to drive and regulate protein targeting. Using real-time fluorescence, we showed that the cargo for SRP--ribosomes translating nascent polypeptides with signal sequences--accelerates SRP.SR complex assembly over 100-fold, thereby driving rapid delivery of cargo to the membrane. A series of subsequent rearrangements in the SRP x SR GTPase complex provide important driving forces to unload the cargo during late stages of protein targeting. Further, the cargo delays GTPase activation in the SRP.SR complex by 8-12 fold, creating an important time window that could further improve the efficiency and fidelity of protein targeting. Thus, the SRP and SR GTPases, without recruiting external regulatory factors, constitute a self-sufficient system that provides exquisite spatial and temporal control of a complex cellular process.

Original languageEnglish
Pages (from-to)1754-9
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number6
DOIs
Publication statusPublished - 10 Feb 2009

Keywords

  • Bacterial Proteins
  • Cell Membrane
  • Escherichia coli Proteins
  • GTP Phosphohydrolases
  • Multiprotein Complexes
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Peptide
  • Ribosomes
  • Signal Recognition Particle

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