PDBsum entry 3ng1

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protein ligands metals Protein-protein interface(s) links
Signal recognition PDB id
Protein chains
294 a.a. *
SO4 ×2
EDO ×4
_CD ×6
Waters ×196
* Residue conservation analysis
PDB id:
Name: Signal recognition
Title: N and gtpase domains of the signal sequence recognition protein ffh from thermus aquaticus
Structure: Signal sequence recognition protein ffh. Chain: a, b. Fragment: ng gtpase fragment. Synonym: ffh. Engineered: yes
Source: Thermus aquaticus. Organism_taxid: 271. Gene: ffh. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.30Å     R-factor:   0.199     R-free:   0.225
Authors: D.M.Freymann,R.M.Stroud,P.Walter
Key ref:
D.M.Freymann et al. (1999). Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP. Nat Struct Biol, 6, 793-801. PubMed id: 10426959 DOI: 10.1038/11572
13-Sep-98     Release date:   30-Jul-99    
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Protein chains
Pfam   ArchSchema ?
O07347  (SRP54_THEAQ) -  Signal recognition particle protein
430 a.a.
294 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     signal recognition particle   1 term 
  Biological process     SRP-dependent cotranslational protein targeting to membrane   1 term 
  Biochemical function     GTP binding     2 terms  


DOI no: 10.1038/11572 Nat Struct Biol 6:793-801 (1999)
PubMed id: 10426959  
Functional changes in the structure of the SRP GTPase on binding GDP and Mg2+GDP.
D.M.Freymann, R.J.Keenan, R.M.Stroud, P.Walter.
Ffh is a component of a bacterial ribonucleoprotein complex homologous to the signal recognition particle (SRP) of eukaryotes. It comprises three domains that mediate both binding to the hydrophobic signal sequence of the nascent polypeptide and the GTP-dependent interaction of Ffh with a structurally homologous GTPase of the SRP receptor. The X-ray structures of the two-domain 'NG' GTPase of Ffh in complex with Mg2+GDP and GDP have been determined at 2.0 A resolution. The structures explain the low nucleotide affinity of Ffh and locate two regions of structural mobility at opposite sides of the nucleotide-binding site. One of these regions includes highly conserved sequence motifs that presumably contribute to the structural trigger signaling the GTP-bound state. The other includes the highly conserved interface between the N and G domains, and supports the hypothesis that the N domain regulates or signals the nucleotide occupancy of the G domain.
  Selected figure(s)  
Figure 3.
Figure 3. Comparison of the GDP-binding interactions in Ffh (G2) with those in Ras (4q21). a, In Ffh, the 'closing loop' wraps around Lys 117 and forms van der Waals contacts with the guanine base. Lys 117 and Thr 114 are bridged by a buried water molecule that forms the floor of the binding site and provides a hydrogen bond to the guanine N7. Motifs I and IV are coupled by interactions of Lys 246 and Thr 245 with carbonyl oxygens of the motif I backbone. b, In Ras, Asn 116 bridges the binding site by hydrogen-bonding the carbonyl oxygen of motif I Val 14 and the hydroxyl of Thr 144 of the G-5 loop. The G-5 loop provides a hydrogen bond from Ala 146 to the guanine O6; similar O6 hydrogen bonding is present in other GTPases, but is absent in Ffh. The hydrophobic character of the floor of the binding site is also typical of most other GTPases (but not the Rho subfamily of GTPases, which includes buried water molecules^46, ^47). A packing interaction structurally analogous to the 'closing loop' in Ffh is provided by Phe 28 from the 1-helix in Ras; in other GTPases, it is provided by elements of the 4 loop.
Figure 5.
Figure 5. Cartoon summarizing the structural consequences of binding of Mg^2+GDP and GDP to NG. The three structures suggest a pathway for stepwise release of Mg^2+ and GDP. GTPase sequence motifs I, II and III interact with the magnesium and phosphate groups. On release of Mg^2+ (or perhaps Mg^2+P[i]) they can form a network of hydrogen bonding interactions that stabilizes the nucleotide-free protein. Gln 144 is adjacent to the active site and can hydrogen bond the -phosphate of the product GDP, thereby opening up the active site for product release. The closing loop, depicted at the bottom of the active site, packs against the bound nucleotide but on nucleotide release moves away and becomes disordered. The position of motif IV, which provides recognition of the guanine base, is coupled to the position of the N domain. The concerted action of the four elements presumably allows regulation of binding and release, and can explain the low nucleotide affinity of the SRP GTPase.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 793-801) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20544960 M.Yang, X.Zhang, and K.Han (2010).
Molecular dynamics simulation of SRP GTPases: towards an understanding of the complex formation from equilibrium fluctuations.
  Proteins, 78, 2222-2237.  
19469550 S.O.Shan, S.L.Schmid, and X.Zhang (2009).
Signal recognition particle (SRP) and SRP receptor: a new paradigm for multistate regulatory GTPases.
  Biochemistry, 48, 6696-6704.  
19174514 X.Zhang, C.Schaffitzel, N.Ban, and S.O.Shan (2009).
Multiple conformational switches in a GTPase complex control co-translational protein targeting.
  Proc Natl Acad Sci U S A, 106, 1754-1759.  
18953414 P.F.Egea, J.Napetschnig, P.Walter, and R.M.Stroud (2008).
Structures of SRP54 and SRP19, the two proteins that organize the ribonucleic core of the signal recognition particle from Pyrococcus furiosus.
  PLoS ONE, 3, e3528.
PDB codes: 3dlu 3dlv 3dm5
18931411 U.D.Ramirez, P.J.Focia, and D.M.Freymann (2008).
Nucleotide-binding flexibility in ultrahigh-resolution structures of the SRP GTPase Ffh.
  Acta Crystallogr D Biol Crystallogr, 64, 1043-1053.
PDB codes: 2c03 2c04
18004774 Y.Agari, S.Sato, T.Wakamatsu, Y.Bessho, A.Ebihara, S.Yokoyama, S.Kuramitsu, and A.Shinkai (2008).
X-ray crystal structure of a hypothetical Sua5 protein from Sulfolobus tokodaii strain 7.
  Proteins, 70, 1108-1111.
PDB code: 2eqa
17151076 C.G.Noble, B.Beuth, and I.A.Taylor (2007).
Structure of a nucleotide-bound Clp1-Pcf11 polyadenylation factor.
  Nucleic Acids Res, 35, 87-99.
PDB code: 2npi
17622352 C.L.Reyes, E.Rutenber, P.Walter, and R.M.Stroud (2007).
X-ray structures of the signal recognition particle receptor reveal targeting cycle intermediates.
  PLoS ONE, 2, e607.
PDB codes: 2q9a 2q9b 2q9c
17186523 J.Gawronski-Salerno, J.S.Coon, P.J.Focia, and D.M.Freymann (2007).
X-ray structure of the T. aquaticus FtsY:GDP complex suggests functional roles for the C-terminal helix of the SRP GTPases.
  Proteins, 66, 984-995.
PDB code: 2iyl
17475780 P.Jaru-Ampornpan, S.Chandrasekar, and S.O.Shan (2007).
Efficient interaction between two GTPases allows the chloroplast SRP pathway to bypass the requirement for an SRP RNA.
  Mol Biol Cell, 18, 2636-2645.  
17682051 S.O.Shan, S.Chandrasekar, and P.Walter (2007).
Conformational changes in the GTPase modules of the signal reception particle and its receptor drive initiation of protein translocation.
  J Cell Biol, 178, 611-620.  
16987964 I.L.Mainprize, D.R.Beniac, E.Falkovskaia, R.M.Cleverley, L.M.Gierasch, F.P.Ottensmeyer, and D.W.Andrews (2006).
The structure of Escherichia coli signal recognition particle revealed by scanning transmission electron microscopy.
  Mol Biol Cell, 17, 5063-5074.  
17139088 U.D.Ramirez, and D.M.Freymann (2006).
Analysis of protein hydration in ultrahigh-resolution structures of the SRP GTPase Ffh.
  Acta Crystallogr D Biol Crystallogr, 62, 1520-1534.
PDB codes: 2j45 2j46
14749771 E.C.Mandon, and R.Gilmore (2004).
GTPase twins in the SRP family.
  Nat Struct Mol Biol, 11, 115-116.  
15166137 E.H.Williams, X.Perez-Martinez, and T.D.Fox (2004).
MrpL36p, a highly diverged L31 ribosomal protein homolog with additional functional domains in Saccharomyces cerevisiae mitochondria.
  Genetics, 167, 65-75.  
15546976 F.Chu, S.O.Shan, D.T.Moustakas, F.Alber, P.F.Egea, R.M.Stroud, P.Walter, and A.L.Burlingame (2004).
Unraveling the interface of signal recognition particle and its receptor by using chemical cross-linking and tandem mass spectrometry.
  Proc Natl Acad Sci U S A, 101, 16454-16459.  
15189152 J.A.Doudna, and R.T.Batey (2004).
Structural insights into the signal recognition particle.
  Annu Rev Biochem, 73, 539-557.  
15523481 K.Wild, M.Halic, I.Sinning, and R.Beckmann (2004).
SRP meets the ribosome.
  Nat Struct Mol Biol, 11, 1049-1053.  
14696184 P.J.Focia, H.Alam, T.Lu, U.D.Ramirez, and D.M.Freymann (2004).
Novel protein and Mg2+ configurations in the Mg2+GDP complex of the SRP GTPase ffh.
  Proteins, 54, 222-230.
PDB code: 1o87
14726591 P.J.Focia, I.V.Shepotinovskaya, J.A.Seidler, and D.M.Freymann (2004).
Heterodimeric GTPase core of the SRP targeting complex.
  Science, 303, 373-377.
PDB code: 1okk
12853463 K.Nagai, C.Oubridge, A.Kuglstatter, E.Menichelli, C.Isel, and L.Jovine (2003).
Structure, function and evolution of the signal recognition particle.
  EMBO J, 22, 3479-3485.  
14657338 K.R.Rosendal, K.Wild, G.Montoya, and I.Sinning (2003).
Crystal structure of the complete core of archaeal signal recognition particle and implications for interdomain communication.
  Proc Natl Acad Sci U S A, 100, 14701-14706.
PDB codes: 1qzw 1qzx
12663860 S.O.Shan, and P.Walter (2003).
Induced nucleotide specificity in a GTPase.
  Proc Natl Acad Sci U S A, 100, 4480-4485.  
12702815 S.Q.Gu, F.Peske, H.J.Wieden, M.V.Rodnina, and W.Wintermeyer (2003).
The signal recognition particle binds to protein L23 at the peptide exit of the Escherichia coli ribosome.
  RNA, 9, 566-573.  
12244111 R.M.Cleverley, and L.M.Gierasch (2002).
Mapping the signal sequence-binding site on SRP reveals a significant role for the NG domain.
  J Biol Chem, 277, 46763-46768.  
11233986 J.R.Jagath, N.B.Matassova, Leeuw, J.M.Warnecke, G.Lentzen, M.V.Rodnina, J.Luirink, and W.Wintermeyer (2001).
Important role of the tetraloop region of 4.5S RNA in SRP binding to its receptor FtsY.
  RNA, 7, 293-301.  
11395422 R.J.Keenan, D.M.Freymann, R.M.Stroud, and P.Walter (2001).
The signal recognition particle.
  Annu Rev Biochem, 70, 755-775.  
11566135 S.Padmanabhan, and D.M.Freymann (2001).
The conformation of bound GMPPNP suggests a mechanism for gating the active site of the SRP GTPase.
  Structure, 9, 859-867.
PDB codes: 1jpj 1jpn
11726508 Y.Lu, H.Y.Qi, J.B.Hyndman, N.D.Ulbrandt, A.Teplyakov, N.Tomasevic, and H.D.Bernstein (2001).
Evidence for a novel GTPase priming step in the SRP protein targeting pathway.
  EMBO J, 20, 6724-6734.  
11123669 A.A.Herskovits, E.S.Bochkareva, and E.Bibi (2000).
New prospects in studying the bacterial signal recognition particle pathway.
  Mol Microbiol, 38, 927-939.  
10970849 B.Prakash, L.Renault, G.J.Praefcke, C.Herrmann, and A.Wittinghofer (2000).
Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanism.
  EMBO J, 19, 4555-4564.
PDB code: 1f5n
10801496 G.Montoya, K.Kaat, R.Moll, G.Schäfer, and I.Sinning (2000).
The crystal structure of the conserved GTPase of SRP54 from the archaeon Acidianus ambivalens and its comparison with related structures suggests a model for the SRP-SRP receptor complex.
  Structure, 8, 515-525.
PDB codes: 1j8m 1j8y
10607673 R.M.Stroud, and P.Walter (1999).
Signal sequence recognition and protein targeting.
  Curr Opin Struct Biol, 9, 754-759.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.