title: Structural Basis for Conserved Regulation and Adaptation of the Signal Recognition Particle Targeting Complex.
abstract: The signal recognition particle (SRP) is a ribonucleoprotein complex with a key role in targeting and insertion of membrane proteins. The two SRP GTPases, SRP54 (Ffh in bacteria) and FtsY (SRα in eukaryotes), form the core of the targeting complex (TC) regulating the SRP cycle. The architecture of the TC and its stimulation by RNA has been described for the bacterial SRP system while this information is lacking for other domains of life. Here, we present the crystal structures of the GTPase heterodimers of archaeal (Sulfolobus solfataricus), eukaryotic (Homo sapiens), and chloroplast (Arabidopsis thaliana) SRP systems. The comprehensive structural comparison combined with Brownian dynamics simulations of TC formation allows for the description of the general blueprint and of specific adaptations of the quasi-symmetric heterodimer. Our work defines conserved external nucleotide-binding sites for SRP GTPase activation by RNA. Structural analyses of the GDP-bound, post-hydrolysis states reveal a conserved, magnesium-sensitive switch within the I-box. Overall, we provide a general model for SRP cycle regulation by RNA.
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Wild
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
authors.forename: Gert
authors.initials: G
authors.lastname: Bange
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloss-Wolfsbrunnenweg 35, D-69118 Heidelberg, Germany.
authors.forename: Domantas
authors.initials: D
authors.lastname: Motiejunas
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Kribelbauer
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hendricks
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Segnitz
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloss-Wolfsbrunnenweg 35, D-69118 Heidelberg, Germany; Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, INF 282, 69120 Heidelberg, Germany.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Wade
authors.affiliation: Heidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, Germany. Electronic address: irmi.sinning@bzh.uni-heidelberg.de.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
mesh_terms: D017360:Arabidopsis / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites / Q000502:physiology; D019281:Dimerization; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D018271:Signal Recognition Particle / Q000737:chemistry* / Q000378:metabolism*; D048229:Sulfolobus solfataricus / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018271:Signal Recognition Particle; D020558:GTP Phosphohydrolases
keywords: SRP GTPase; X-ray structure analysis; co-translational protein targeting; molecular modeling; ribonucleoprotein complex