SRP RNA remodeling by SRP68 explains its role in protein translocation.
The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an α-helical arginine-rich motif (ARM) into the major groove. The ARM opens the conserved 5f RNA loop, which in ribosome-bound SRP establishes a contact to ribosomal RNA. Our data provide the structural basis for eukaryote-specific, SRP68-driven RNA remodeling required for protein translocation.
Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
Jan Timo
JT
Grotwinkel
Klemens
K
Wild
Bernd
B
Segnitz
Irmgard
I
Sinning
D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000737:chemistry* / Q000378:metabolism*; D012270:Ribosomes; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C115990:7SL RNA; D012335:RNA, Ribosomal; D020733:RNA, Small Cytoplasmic; C117074:SRP19 protein, human; C512269:SRP68 protein, human; D018271:Signal Recognition Particle