Medical College of Wisconsin
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Molecular mechanism of GTPase activation at the signal recognition particle (SRP) RNA distal end. J Biol Chem 2013 Dec 20;288(51):36385-97

Date

10/24/2013

Pubmed ID

24151069

Pubmed Central ID

PMC3868752

DOI

10.1074/jbc.M113.513614

Scopus ID

2-s2.0-84890891983 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

The signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the SRP RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the SRP and SRP receptor, this GTPase complex subsequently relocalizes ∼100 Å to the 5',3'-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover. Here we combined biochemical, single molecule, and NMR studies to investigate the molecular mechanism of this large scale conformational change. We show that two independent sites contribute to the interaction of the GTPase complex with the SRP RNA distal end. Loop E plays a crucial role in the precise positioning of the GTPase complex on these two sites by inducing a defined bend in the RNA helix and thus generating a preorganized recognition surface. GTPase docking can be uncoupled from its subsequent activation, which is mediated by conserved bases in the next internal loop. These results, combined with recent structural work, elucidate how the SRP RNA induces GTPase relocalization and activation at the end of the protein targeting reaction.

Author List

Shen K, Wang Y, Hwang Fu YH, Zhang Q, Feigon J, Shan SO

Author

Yaqiang Wang PhD, MS Assistant Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Bacterial Proteins
Base Sequence
Escherichia coli
Escherichia coli Proteins
GTP Phosphohydrolases
Molecular Docking Simulation
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
Protein Binding
RNA, Small Cytoplasmic
Receptors, Cytoplasmic and Nuclear
Signal Recognition Particle