Abstract
The signal recognition particle (SRP) and its conjugate receptor (SR) mediate cotranslational targeting of a subclass of proteins destined for secretion to the endoplasmic reticulum membrane in eukaryotes or to the plasma membrane in prokaryotes. Conserved active site residues in the GTPase domains of both SRP and SR mediate discrete conformational changes during formation and dissociation of the SRP.SR complex. Here, we describe structures of the prokaryotic SR, FtsY, as an apo protein and in two different complexes with a non-hydrolysable GTP analog (GMPPNP). These structures reveal intermediate conformations of FtsY containing GMPPNP and explain how the conserved active site residues position the nucleotide into a non-catalytic conformation. The basis for the lower specificity of binding of nucleotide in FtsY prior to heterodimerization with the SRP conjugate Ffh is also shown. We propose that these structural changes represent discrete conformational states assumed by FtsY during targeting complex formation and dissociation.
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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Catalytic Domain
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Cell Cycle / physiology*
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Dimerization
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Endoplasmic Reticulum / physiology
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GTP Phosphohydrolases / metabolism
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Guanylyl Imidodiphosphate / metabolism
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Kinetics
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Models, Molecular
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Nucleotides / metabolism
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Protein Binding
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Protein Biosynthesis
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Proteins / genetics
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Receptors, Cytoplasmic and Nuclear / chemistry*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Peptide / chemistry*
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism
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Signal Recognition Particle / chemistry
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Signal Recognition Particle / genetics
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Signal Recognition Particle / metabolism
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Substrate Specificity
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Thermus / metabolism
Substances
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Bacterial Proteins
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FtsY protein, Bacteria
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Nucleotides
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Proteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, Peptide
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Signal Recognition Particle
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signal peptide receptor
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Guanylyl Imidodiphosphate
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GTP Phosphohydrolases