Structure of the signal recognition particle interacting with the elongation-arrested ribosome.
Cotranslational translocation of proteins across or into membranes is a vital process in all kingdoms of life. It requires that the translating ribosome be targeted to the membrane by the signal recognition particle (SRP), an evolutionarily conserved ribonucleoprotein particle. SRP recognizes signal sequences of nascent protein chains emerging from the ribosome. Subsequent binding of SRP leads to a pause in peptide elongation and to the ribosome docking to the membrane-bound SRP receptor. Here we present the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, solved to 12 A by cryo-electron microscopy, enables us to generate a molecular model of SRP in its functional conformation. The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.
Institute of Biochemistry, Charité, University Medical School, Humboldt University of Berlin, Monbijoustrasse 2, 10117 Berlin, Germany.
Mario
M
Halic
Thomas
T
Becker
Martin R
MR
Pool
Christian M T
CM
Spahn
Robert A
RA
Grassucci
Joachim
J
Frank
Roland
R
Beckmann
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D008322:Mammals; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010441:Peptide Chain Elongation, Translational; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D013329:Structure-Activity Relationship
D021382:Protein Sorting Signals; D018271:Signal Recognition Particle