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.
