title: A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel.
abstract: Sorting of eukaryotic membrane and secretory proteins depends on recognition of ribosome-bound nascent chain signal sequences by the signal recognition particle (SRP). The current model suggests that the SRP cycle is initiated when a signal sequence emerges from the ribosomal tunnel and binds to SRP. Then elongation is slowed until the SRP-bound ribosome-nascent chain complex (RNC) is targeted to the SRP receptor in the endoplasmic reticulum (ER) membrane. The RNC is then transferred to the translocon, SRP is released, and translation resumes. Because RNCs do not target to the translocon efficiently if nascent chains become too long, the window for SRP to identify its substrates is short. We now show that a transmembrane signal-anchor sequence (SA) significantly enhances binding of SRP to RNCs even before the SA emerges from the ribosomal tunnel. In this mode, SRP does not contact the SA directly but is in close proximity to the portion of the nascent polypeptide that has already left the ribosomal tunnel. Early recruitment of SRP provides a mechanism to expand the window for substrate identification. We suggest that the dynamics of the SRP-ribosome interaction is affected not only by the direct binding of SRP to an exposed signal sequence but also by properties of the translating ribosome that are triggered from within the tunnel.
authors.affiliation: Institute of Biochemistry and Molecular Biology and Center for Biological Signalling Studies, University of Freiburg, Stefan-Meier-Strasse 17, D-79104 Freiburg, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Berndt
authors.forename: Stefan
authors.initials: S
authors.lastname: Oellerer
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Johnson
authors.forename: Sabine
authors.initials: S
authors.lastname: Rospert
mesh_terms: D019943:Amino Acid Substitution; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals; D012270:Ribosomes / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018832:Molecular Chaperones; D021382:Protein Sorting Signals; D018271:Signal Recognition Particle