title: Signal-sequence induced conformational changes in the signal recognition particle.
abstract: Co-translational protein targeting is an essential, evolutionarily conserved pathway for delivering nascent proteins to the proper cellular membrane. In this pathway, the signal recognition particle (SRP) first recognizes the N-terminal signal sequence of nascent proteins and subsequently interacts with the SRP receptor. For this, signal sequence binding in the SRP54 M domain must be effectively communicated to the SRP54 NG domain that interacts with the receptor. Here we present the 2.9 Å crystal structure of unbound- and signal sequence bound SRP forms, both present in the asymmetric unit. The structures provide evidence for a coupled binding and folding mechanism in which signal sequence binding induces the concerted folding of the GM linker helix, the finger loop, and the C-terminal alpha helix αM6. This mechanism allows for a high degree of structural adaptability of the binding site and suggests how signal sequence binding in the M domain is coupled to repositioning of the NG domain.
authors.affiliation: Department of Chemistry, Umeå University, Umeå SE-901 87, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hainzl
authors.affiliation: Department of Chemistry, Umeå University, Umeå SE-901 87, Sweden.
authors.forename: A Elisabeth
authors.initials: AE
authors.lastname: Sauer-Eriksson
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry*; D063747:Methanocaldococcus / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D021382:Protein Sorting Signals; D018271:Signal Recognition Particle / Q000737:chemistry*
chemical_list: D019843:Archaeal Proteins; D021382:Protein Sorting Signals; D018271:Signal Recognition Particle