3.6.5.4	evolution	co-evolution of two GTPases enables efficient protein targeting in an RNA-less chloroplast signal recognition particle pathway	757189	
3.6.5.4	evolution	SR ribosome binding is evolutionarily conserved	757758	
3.6.5.4	evolution	SR ribosome binding is evolutionarily conserved. Unlike the ribosome-binding activity of human SRalpha, CtSRalpha is unable to destabilize the interaction between protein translocase subunit Sec61beta and the Sec translocase-associated endoplasmic reticulum membrane protein Sec62, suggesting that this interaction is specific to higher eukaryotes	-, 757758	
3.6.5.4	evolution	the signal recognition particle receptor SRbeta belongs to the Ras-family of small monomeric GTPases, specific differences to the Arf and Sar1 families with implications for GTPase regulation are determined, overview. SRbeta is the oldest member of all small GTPases branching first in eukaryotic evolution	-, 758481	
3.6.5.4	malfunction	asymmetries in the catalytic center affect GTP hydrolysis, overview	758489	
3.6.5.4	malfunction	deletion of the finger loop abolishes loading of the cpSRP cargo, light-harvesting chlorophyll binding protein	756198	
3.6.5.4	malfunction	deletion of the N-terminal transmembrane domain of SRbeta does not effect receptor dimerization but reveals a cryptic translocation signal that overlaps the GTPase domain. Deletion of the G-1 region, (SRbetaD5) which comprises part of the SRbeta GTPase domain, abolishes binding to SRalpha. A mutant SRbeta containing an amino acid substitution allows the GTPase domain to bind XTP dimerizes with SRalpha most efficiently in the presence of XTP or XDP, but not ATP	757430	
3.6.5.4	malfunction	in contrast to the Sec61beta-SRalpha cross-link species, which increase in abundance when SR is added to EKRMs (membranes stripped of ribosomes with EDTA and high salt), most other Sec61beta-derived cross-linked adducts are reduced, in particular, the cross-link between Sec61beta and Sec62. A mutant SRP receptor, which contains only the SRX domain of SRalpha (SRalpha126/betaDN), shows a much weaker reduction in Sec61beta-Sec62 crosslinking	757758	
3.6.5.4	metabolism	in prokaryotic cells, the signal recognition particle consists of a SRP54 protein or Ffh and a 4.5S SRP RNA. Ffh contains a methionine-rich M domain, which binds the SRP RNA and the signal sequence on the translating ribosome. In addition, an NG domain in Ffh, comprising a GTPase G domain and a four-helix bundle N domain, forms a tight complex with a highly homologous NG domain in the SRP receptor, called FtsY in bacteria, in the presence of GTP. GTP hydrolysis at the end of the signal recognition particle cycle drives the disassembly of the Ffh-FtsY GTPase complex. The assembly of the signal recognition particle-FtsY GTPase complex and its GTPase activation require discrete conformational rearrangements in the signal recognition particle that are regulated by the RNC and the target membrane, respectively, thus ensuring the spatial and temporal precision of these molecular events during protein targeting, function of SRP RNA during co-translational protein targeting, overiew	734245	
3.6.5.4	metabolism	two distinct pathways deliver secretory proteins to the Sec61 protein translocase in the endoplasmic reticulum (ER) membrane. The canonical pathway requires the signal recognition particle (SRP) and its cognate receptor (SR), and targets ribosome-associated proteins to the Sec translocase. The SRP-independent pathway requires the Sec translocase-associated ER membrane protein Sec62 and can be uncoupled from translation. SR switches translocons to SRP-dependent translocation by displacing Sec62. This activity localizes to the charged linker region between the longin and GTPase domains of SRalpha. A second pathway promotes ribosome binding and is conserved between all eukaryotes. These specific regions in SRalpha reprogramme the Sec translocon and facilitate recruitment of ribosome-nascent chain complexes	757758	
3.6.5.4	additional information	analysis of binding of wild-type and mutant SRalpha and SRbeta by gel filtration and immunoprecipitation, overview. SRX2, the minimum SRbeta binding domain of SRalpha, binds to the GTPase domain of SRbeta, no other regions of SRalpha are observed to bind to SRbeta. Structural basis for conserved regulation and adaptation of the signal recognition particle targeting complex, overview	757430	
3.6.5.4	additional information	analysis of the G-loop dynamics of FtsY NG domain, overview. The combination of high-resolution and multiple solved structures of FtsYNG in different states reveals a distinct sensor-relay system of the unique GTPase receptor. A nucleotide sensing function of the P-loop assists FtsYNG in nucleotide-binding and contributes to modulate nucleotide binding properties in SRP GTPases. A reorganization of the other G-loops and the insertion binding domain (IBD) is observed only upon transition from a diphosphate to a triphosphate nucleotide. The binding of magnesium in the nucleotide site causes the reorientation of the beta-and gamma-phosphate groups toward the jaws of the P-loop and stabilizes the binding of the nucleotide, creating a network of hydrogen and water-bridge interactions. An alternative conformation of the P-loop senses nucleotide-binding, FtsY P-loops dynamics, mechanism, detailed overview	757514	
3.6.5.4	additional information	bidentate interaction between the Ffh-FtsY GTPase complex and the distal end of the SRP RNA, overview. By modifying the GTPase docking interface, the efficiency of activation of the Ffh-FtsY GTPase complex can be specifically tuned. A guanine at residue 86 could compete with and substitute for G83 as a catalytic base. Conserved bases in loop D specifically catalyze GTP hydrolysis, a guanine at residue 86 can compete with and substitute for G83 as a catalytic base, loop E controls the action of the distal end docking sites	734245	
3.6.5.4	additional information	binding of SR to Sec61 positions SRalpha close to Sec61beta	757758	
3.6.5.4	additional information	concerted complex assembly and GTPase activation occurs in the chloroplast signal recognition particle. In contrast to the cytosolic homologues, GTPase activation in the chloroplast SRP-SR complex contributes marginally to the targeting of LHC proteins. Complex assembly and GTPase activation are highly coupled in the chloroplast SRP and SR and suggest that the chloroplast GTPases may forego the GTPase activation step as a key regulatory point. Homology model of the cpSRP54·cpFtsY complex based on superposition of the crystal structure of apo-cpFtsY onto that of Thermus aquaticus SR, i.e. FtsY, in complex with Ffh. Thermodynamic and kinetics for formation of the cpSRP54-cpFtsY complex, formed by wild-types and mutants, detailed overview. IBD loops play essential roles in both complex assembly and GTPase activation	718911	
3.6.5.4	additional information	efficient protein targeting requires heterodimerization and activation of the GTPases present in the SRP receptor FtsY and the SRP protein Ffh. FtsY also forms a homodimer at the membrane, in vitro and in vivo, using the same interaction surface as the heterodimer. Homodimerization adds to the complex interaction landscape of protein targeting. SRP binding to the receptor occurs by heterodimerization of the highly conserved NG domains of Ffh and FtsY, respectively, resulting in the formation of the so-called targeting complex. A dimerization-induced conformational switch of the nucleotide gamma-phosphate is conserved in Escherichia coli, filling an important gap in SRP GTPase activation. Asymmetries in the catalytic center affect GTP hydrolysis	758489	
3.6.5.4	additional information	reconstitution of the human SRP system and quantitative and systematic analysis of its ribosome interactions, as well as interactions within the SRP complex, overview. SRP RNA does not bind to the ribosome, while signal recognition particle (SRP) binds with nanomolar affinity involving a two-step mechanism of the key-player SRP GTPase, SRP54. SRP54 is the major determinant of SRP-ribosome interaction. Modulation of SRP-ribosome interaction by signal recognition particle receptor (SR). As long as SRP54 is not assembled into SRP, ribosome binding is of moderate affinity at most. Separating SRP biogenesis in two parts, a nucleolar and a cytosolic one, is essential for correct SRP assembly. Affinity of the entire recombinant SRPS/SR system to RNCs exposing an SRP-targeting signal	757857	
3.6.5.4	additional information	the chloroplast signal recognition particle (cpSRP) is a heterodimer composed of an evolutionarily conserved 54-kDa GTPase (cpSRP54) and a unique 43-kDa subunit (cpSRP43) responsible for delivering light harvesting chlorophyll binding protein to the thylakoid membrane. Determination of in silico three-dimensional model of the structure of cpSRP54 by homology modeling using cytosolic homologues, overview. Single-molecule Foerster resonance energy transfer experiments reveals the presence of at least two distinct conformations. Small angle X-ray scattering shows that the linking region among the GTPase (G-domain) and methionine-rich (M-domain) domains, an M-domain loop, and the cpSRP43 binding C-terminal extension of cpSRP54 are predominantly disordered. The linker and loop segments are observed to play an important role in organizing the domain arrangement of cpSRP54	756198	
3.6.5.4	additional information	the SRP RNAis a universally conserved component of SRP that mediates key interactions between two GTPases in SRP and its receptor, thus enabling rapid delivery of cargo to the target membrane. Notably, this essential RNA is bypassed in the chloroplast (cp) SRP of green plants. The cpSRP and cpSRP receptor GTPases (cpSRP54 and cpFtsY, respectively) interact efficiently by themselves without the SRP RNA, molecular mechanism, overview	757189	
3.6.5.4	additional information	the structures of the SRbeta-GTPase in its GTP- and GDP-states describe a switch cycle revealing a fixed switch II region. The linker region between the N-terminal SRX domain and the C-terminal NG domain of SRalpha is crucial for ribosome binding of the SR. Analysis of the structure of the ctSRbeta-GTP/SRX complex and of ctSRbeta-GDP complex, overview. The conformation of SRbeta does not directly influence ribosome binding but rather regulates the SRX interaction during the switch cycle. ctSRbeta contains all consensus fingerprints that define the SRbeta family, which like for all GTPases cluster around the nucleotide. The fingerprints are GxxxxGKS/T64 for the P loop, TxxS107 within the switch I region (residues 99-110), DxPGHxxLR154 within the switch II region (residues 146-160), and NKxD253 for the guanine binding pocket. The catalytic residue His150 is in a resting position pointing outward of the active center, rendering the ctSRbeta-GTP/SRX complex inactive. The histidine is tied to the backbone nitrogen of Lys152 within switch II and therefore it must be available in the deprotonated form. A unique feature of SRbeta applies to the switch II fingerprint. The conserved fingerprint within Arf and Sar1 writes as DxGG(QArf/HSar1)xxxRxW, and this signature is the prerequisite for the family-specific interswitch toggle mechanism. While most of the fingerprint is conserved in the SRb family, the first glycine is replaced by the rigid proline and the terminal tryptophan is not present. CtSRX not only contacts switch I, but also interacts with the N-terminal turn of helix alpga2 (HxxL153) in the switch II region. Most importantly, the C-terminal Pi-helical turn of helix alpha1x (X1xxFFX2) sequesters the catalytic histidine His150 away from the active center	-, 758481	
3.6.5.4	physiological function	co-translational protein targeting to membranes depends on the regulated interaction of two ribonucleoprotein particles (RNPs): the ribosome and the signal recognition particle (SRP). Human SRP is composed of an SRP RNA and six proteins with the SRP GTPase SRP54 forming the targeting complex with the heterodimeric SRP receptor (SRalphabeta) at the endoplasmic reticulum membrane	757857	
3.6.5.4	physiological function	important structural dynamics relevant to cpSRP54's role in the post- and co-translational signaling processes	756198	
3.6.5.4	physiological function	the enzyme is involved in translocation of the signal recognition particle (SRP) RNA is a universally conserved and essential component of the SRP that mediates the co-translational targeting of proteins to the correct cellular membrane. During the targeting reaction, two functional ends in the signal recognition particle RNA mediate distinct functions. Whereas the RNA tetraloop facilitates initial assembly of two GTPases between the signal recognition particle and signal recognition particle receptor, this GTPase complex subsequently relocalizes about 100 A to the 5',3'-distal end of the RNA, a conformation crucial for GTPase activation and cargo handover	734245	
3.6.5.4	physiological function	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 (SRalpha 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	757430	
3.6.5.4	physiological function	the signal recognition particle (SRP) is an essential ribonucleoprotein particle that mediates the co-translational targeting of newly synthesized proteins to cellular membranes	757189	
3.6.5.4	physiological function	the signal recognition particle receptor (SR) targets nascent protein chains to the endoplasmic reticulum. The eukaryotic SR consists of the two GTPases SRalpha and SRbeta. SRbeta-GTP interacts with ribosomes only in presence of SRalpha	-, 758481	
3.6.5.4	physiological function	the universally conserved signal recognition particle, SRP, and SRP receptor, SR, mediate the cotranslational targeting of proteins to cellular membranes. In contrast, a unique chloroplast SRP in green plants is primarily dedicated to the post-translational targeting of light harvesting chlorophyll a/b binding proteins. In both pathways, dimerization and activation between the SRP and SR GTPases mediate the delivery of cargo. Efficient assembly of the cpSRP54-cpFtsY complex is crucial for the targeting and integration of LHCP, whereas GTPase activation and/or GTP hydrolysis plays a modulatory role to help enhance the efficiency of targeting	718911	
3.6.5.4	physiological function	together with its receptor SR, signal recognition particle, SRP, mediates the GTP-dependent delivery of translating ribosomes bearing signal sequences to translocons on the target membrane. The activated SRP:SR GTPase complex binds the distal end of the SRP hairpin RNA where GTP hydrolysis is stimulated. The SRP:SR GTPase complex initially assembles at the tetraloop end of the SRP RNA and then relocalizes to the opposite end of the RNA. This rearrangement provides a mechanism for coupling GTP hydrolysis to the handover of cargo to the translocon	721054	
3.6.5.4	physiological function	two distinct pathways deliver secretory proteins to the Sec61 protein translocase in the endoplasmic reticulum (ER) membrane. The canonical pathway requires the signal recognition particle (SRP) and its cognate receptor (SR), and targets ribosome-associated proteins to the Sec translocase. The SRP-independent pathway requires the Sec translocase-associated ER membrane protein Sec62 and can be uncoupled from translation. SR switches translocons to SRP-dependent translocation by displacing Sec62. This activity localizes to the charged linker region between the longin and GTPase domains of SRalpha. Both SRalpha and SRbeta are GTPases. SR inhibits translocation of Sec62-dependent substrates	757758