Abstract
Cotranslational targeting of membrane and secretory proteins is mediated by the universally conserved signal recognition particle (SRP). Together with its receptor (SR), SRP mediates the guanine triphosphate (GTP)-dependent delivery of translating ribosomes bearing signal sequences to translocons on the target membrane. Here, we present the crystal structure of the SRP:SR complex at 3.9 angstrom resolution and biochemical data revealing that the activated SRP:SR guanine triphosphatase (GTPase) complex binds the distal end of the SRP hairpin RNA where GTP hydrolysis is stimulated. Combined with previous findings, these results suggest that the SRP:SR GTPase complex initially assembles at the tetraloop end of the SRP RNA and then relocalizes to the opposite end of the RNA. This rearrangement provides a mechanism for coupling GTP hydrolysis to the handover of cargo to the translocon.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Proteins / chemistry*
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Bacterial Proteins / metabolism
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Base Sequence
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Binding Sites
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Crystallization
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Crystallography, X-Ray
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Enzyme Activation
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Escherichia coli / chemistry
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Escherichia coli / metabolism
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / metabolism
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GTP Phosphohydrolases / chemistry
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GTP Phosphohydrolases / metabolism
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Guanosine Triphosphate / analogs & derivatives
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Guanosine Triphosphate / chemistry
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Guanosine Triphosphate / metabolism
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Hydrogen Bonding
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Hydrophobic and Hydrophilic Interactions
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Models, Biological
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Models, Molecular
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Nucleic Acid Conformation
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Protein Conformation
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Protein Multimerization
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Protein Structure, Tertiary
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Protein Transport
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RNA, Bacterial / chemistry*
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RNA, Bacterial / metabolism
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Receptors, Cytoplasmic and Nuclear / chemistry*
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Receptors, Cytoplasmic and Nuclear / metabolism
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Ribosomal Proteins / chemistry
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Ribosomal Proteins / metabolism
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Ribosomes / metabolism
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Signal Recognition Particle / chemistry*
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Signal Recognition Particle / metabolism
Substances
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4.5S RNA
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Bacterial Proteins
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Escherichia coli Proteins
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Ffh protein, E coli
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FtsY protein, Bacteria
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RNA, Bacterial
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Receptors, Cytoplasmic and Nuclear
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Ribosomal Proteins
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Signal Recognition Particle
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ribosomal protein L23, E coli
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ribosomal protein L29
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5'-guanylylmethylenebisphosphonate
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Guanosine Triphosphate
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GTP Phosphohydrolases