Lipid activation of the signal recognition particle receptor provides spatial coordination of protein targeting.
The signal recognition particle (SRP) and SRP receptor comprise the major cellular machinery that mediates the cotranslational targeting of proteins to cellular membranes. It remains unclear how the delivery of cargos to the target membrane is spatially coordinated. We show here that phospholipid binding drives important conformational rearrangements that activate the bacterial SRP receptor FtsY and the SRP-FtsY complex. This leads to accelerated SRP-FtsY complex assembly, and allows the SRP-FtsY complex to more efficiently unload cargo proteins. Likewise, formation of an active SRP-FtsY GTPase complex exposes FtsY's lipid-binding helix and enables stable membrane association of the targeting complex. Thus, membrane binding, complex assembly with SRP, and cargo unloading are inextricably linked to each other via conformational changes in FtsY. These allosteric communications allow the membrane delivery of cargo proteins to be efficiently coupled to their subsequent unloading and translocation, thus providing spatial coordination during protein targeting.
Lam
Vinh Q
VQ
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Akopian
David
D
Rome
Michael
M
Henningsen
Doug
D
Shan
Shu-ou
SO
D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D000838:Anions; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C087406:FtsY protein, Bacteria; D010743:Phospholipids; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D018271:Signal Recognition Particle; C036318:signal peptide receptor; D020558:GTP Phosphohydrolases