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PDBsum entry 3cf5
Go to PDB code: 
protein dna_rna metals Protein-protein interface(s) links
Ribosome/antibiotic PDB id
3cf5
Contents
Protein chains
53 a.a.* *
46 a.a.* *
63 a.a.* *
37 a.a. *
19 a.a. *
240 a.a. *
205 a.a. *
197 a.a. *
177 a.a. *
171 a.a. *
144 a.a. *
142 a.a. *
134 a.a. *
141 a.a. *
136 a.a. *
113 a.a. *
104 a.a. *
108 a.a. *
117 a.a. *
94 a.a. *
127 a.a. *
93 a.a. *
110 a.a. *
175 a.a. *
84 a.a. *
72 a.a. *
66 a.a. *
55 a.a. *
58 a.a. *
DNA/RNA
Metals
_MG ×36
* Residue conservation analysis
* C-alpha coords only
PDB id:
3cf5
Name: Ribosome/antibiotic
Title: Thiopeptide antibiotic thiostrepton bound to the large ribosomal subunit of deinococcus radiodurans
Structure: 50s ribosomal protein l33. Chain: 1. 50s ribosomal protein l34. Chain: 2. 50s ribosomal protein l35. Chain: 3. 50s ribosomal protein l36. Chain: 4. Thiostrepton.
Source: Deinococcus radiodurans. Organism_taxid: 1299. Streptomyces azureus. Organism_taxid: 146537. Organism_taxid: 1299
Resolution:
3.30Å     R-factor:   0.276     R-free:   0.318
Authors: J.M.Harms,D.N.Wilson,F.Schluenzen,S.R.Connell,T.Stachelhaus, Z.Zaborowska,C.M.T.Spahn,P.Fucini
Key ref:
J.M.Harms et al. (2008). Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Mol Cell, 30, 26-38. PubMed id: 18406324 DOI: 10.1016/j.molcel.2008.01.009
Date:
02-Mar-08     Release date:   17-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9RSS4  (RL33_DEIRA) -  Large ribosomal subunit protein bL33 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		55 a.a.
53 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSH2  (RL34_DEIRA) -  Large ribosomal subunit protein bL34 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		47 a.a.
46 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW6  (RL35_DEIRA) -  Large ribosomal subunit protein bL35 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		66 a.a.
63 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK0  (RL36_DEIRA) -  Large ribosomal subunit protein bL36 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		37 a.a.
37 a.a.
Protein chain
P0C8P8  (THCL_STRAJ) -  Thiostrepton from Streptomyces azureus
Protein chain
Pfam   ArchSchema ?
Q9RXJ9  (RL2_DEIRA) -  Large ribosomal subunit protein uL2 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		275 a.a.
240 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK2  (RL3_DEIRA) -  Large ribosomal subunit protein uL3 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		211 a.a.
205 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK1  (RL4_DEIRA) -  Large ribosomal subunit protein uL4 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		205 a.a.
197 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ0  (RL5_DEIRA) -  Large ribosomal subunit protein uL5 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		180 a.a.
177 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL3  (RL6_DEIRA) -  Large ribosomal subunit protein uL6 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		185 a.a.
171 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSS7  (RL11_DEIRA) -  Large ribosomal subunit protein uL11 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		144 a.a.
144 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXY1  (RL13_DEIRA) -  Large ribosomal subunit protein uL13 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		174 a.a.
142 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ2  (RL14_DEIRA) -  Large ribosomal subunit protein uL14 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		134 a.a.
134 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSK9  (RL15_DEIRA) -  Large ribosomal subunit protein uL15 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		156 a.a.
141 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ5  (RL16_DEIRA) -  Large ribosomal subunit protein uL16 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		141 a.a.
136 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSJ5  (RL17_DEIRA) -  Large ribosomal subunit protein bL17 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		116 a.a.
113 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL2  (RL18_DEIRA) -  Large ribosomal subunit protein uL18 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		114 a.a.
104 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RWB4  (RL19_DEIRA) -  Large ribosomal subunit protein bL19 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		166 a.a.
108 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSW7  (RL20_DEIRA) -  Large ribosomal subunit protein bL20 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		118 a.a.
117 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY64  (RL21_DEIRA) -  Large ribosomal subunit protein bL21 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		100 a.a.
94 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ7  (RL22_DEIRA) -  Large ribosomal subunit protein uL22 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		134 a.a.
127 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXK0  (RL23_DEIRA) -  Large ribosomal subunit protein uL23 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		95 a.a.
93 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ1  (RL24_DEIRA) -  Large ribosomal subunit protein uL24 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		115 a.a.
110 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RX88  (RL25_DEIRA) -  Large ribosomal subunit protein bL25 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		237 a.a.
175 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RY65  (RL27_DEIRA) -  Large ribosomal subunit protein bL27 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		91 a.a.
84 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RRG8  (RL28_DEIRA) -  Large ribosomal subunit protein bL28 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		81 a.a.
72 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RXJ4  (RL29_DEIRA) -  Large ribosomal subunit protein uL29 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		67 a.a.
66 a.a.
Protein chain
Pfam   ArchSchema ?
Q9RSL0  (RL30_DEIRA) -  Large ribosomal subunit protein uL30 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		55 a.a.
55 a.a.
Protein chain
Pfam   ArchSchema ?
P49228  (RL32_DEIRA) -  Large ribosomal subunit protein bL32 from Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / CCUG 27074 / LMG 4051 / NBRC 15346 / NCIMB 9279 / VKM B-1422 / R1)
Seq:
Struc: 		60 a.a.
58 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

DNA/RNA chains
  G-G-U-C-A-A-G-A-U-A-G-U-A-A-G-G-G-U-C-C-A-C-G-G-U-G-G-A-U-G-C-C-C-U-G-G-C-G-C- ... 2686 bases
  C-A-C-C-C-C-C-G-U-G-C-C-C-A-U-A-G-C-A-C-U-G-U-G-G-A-A-C-C-A-C-C-C-C-A-C-C-C-C- 122 bases

 

 
    reference    
 
 
DOI no: 10.1016/j.molcel.2008.01.009 Mol Cell 30:26-38 (2008)
PubMed id: 18406324  
 
 
Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin.
J.M.Harms, D.N.Wilson, F.Schluenzen, S.R.Connell, T.Stachelhaus, Z.Zaborowska, C.M.Spahn, P.Fucini.
 
  ABSTRACT  
 
The thiopeptide class of antibiotics targets the GTPase-associated center (GAC) of the ribosome to inhibit translation factor function. Using X-ray crystallography, we have determined the binding sites of thiostrepton (Thio), nosiheptide (Nosi), and micrococcin (Micro), on the Deinococcus radiodurans large ribosomal subunit. The thiopeptides, by binding within a cleft located between the ribosomal protein L11 and helices 43 and 44 of the 23S rRNA, overlap with the position of domain V of EF-G, thus explaining how this class of drugs perturbs translation factor binding to the ribosome. The presence of Micro leads to additional density for the C-terminal domain (CTD) of L7, adjacent to and interacting with L11. The results suggest that L11 acts as a molecular switch to control L7 binding and plays a pivotal role in positioning one L7-CTD monomer on the G' subdomain of EF-G to regulate EF-G turnover during protein synthesis.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Binding Position of Thio and Nosi on the 50S Subunit
(A) Overview of thiopeptide binding site on the D. radiodurans 50S subunit. Interface view of the 50S subunit (rRNA and r-proteins colored light and dark blue, respectively) with the thiopeptide binding site boxed. Enlargement of boxed region reveals that the thiopeptides Thio (cyan) and Nosi (green) bind within a cleft between the N-terminal domain (NTD) of r-protein L11 (yellow) and the 23S rRNA H43 and H44 (orange).
(B and C) 2mF[o] − DF[c] σ[A]-weighted difference electron density maps (meshed) contoured to 2σ with (B) Thio, (C) Nosi, L11-NTD, and H44 colored as in (A). 		Figure 6.
Figure 6. Schematic for EF-G and Thiopeptide Action during Translation
(A–D) Model for events leading to EF-G accommodation on the ribosome and Pi release as described in the text. Effect of (E) Thio (purple) and (F) Micro (brown) are also shown schematically. Individual domains of EF-G (orange) are labeled with II-V and G/G′, and the stalk base (SB) components are indicated with L11 (green) divided into with N- and C-terminal domains (NTD, CTD) and rRNA helices H43 and H44 (blue). The C-terminal domain of L7 (L7-CTD) is shown in red. Note that for simplicity, the switching mechanism has been divided into two distinct steps; however, it is unclear as to whether they are sequential, as shown here, or occur simultaneously.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2008, 30, 26-38) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22407015 L.Wang, F.Yang, D.Zhang, Z.Chen, R.M.Xu, K.H.Nierhaus, W.Gong, and Y.Qin (2012).
A conserved proline switch on the ribosome facilitates the recruitment and binding of trGTPases.
  Nat Struct Mol Biol, 19, 403-410.  
21154411 A.W.Barb, J.R.Cort, J.Seetharaman, S.Lew, H.W.Lee, T.Acton, R.Xiao, M.A.Kennedy, L.Tong, G.T.Montelione, and J.H.Prestegard (2011).
Structures of domains I and IV from YbbR are representative of a widely distributed protein family.
  Protein Sci, 20, 396-405.
PDB codes: 2kpu 2l3u 2l5n
21107477 C.Li, F.Zhang, and W.L.Kelly (2011).
Heterologous production of thiostrepton A and biosynthetic engineering of thiostrepton analogs.
  Mol Biosyst, 7, 82-90.  
20111801 C.Li, and W.L.Kelly (2010).
Recent advances in thiopeptide antibiotic biosynthesis.
  Nat Prod Rep, 27, 153-164.  
20121095 C.T.Walsh, and M.A.Fischbach (2010).
Natural products version 2.0: connecting genes to molecules.
  J Am Chem Soc, 132, 2469-2493.  
20494981 H.David-Eden, A.S.Mankin, and Y.Mandel-Gutfreund (2010).
Structural signatures of antibiotic binding sites on the ribosome.
  Nucleic Acids Res, 38, 5982-5994.  
20215430 L.García-Ortega, E.Alvarez-García, J.G.Gavilanes, A.Martínez-del-Pozo, and S.Joseph (2010).
Cleavage of the sarcin-ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding.
  Nucleic Acids Res, 38, 4108-4119.  
20179875 M.A.Ciufolini, and D.Lefranc (2010).
Micrococcin P1: structure, biology and synthesis.
  Nat Prod Rep, 27, 330-342.  
20553602 S.Kirillova, S.C.Tosatto, and O.Carugo (2010).
FRASS: the web-server for RNA structural comparison.
  BMC Bioinformatics, 11, 327.  
19875082 A.L.Starosta, H.Qin, A.Mikolajka, G.Y.Leung, K.Schwinghammer, K.C.Nicolaou, D.Y.Chen, B.S.Cooperman, and D.N.Wilson (2009).
Identification of distinct thiopeptide-antibiotic precursor lead compounds using translation machinery assays.
  Chem Biol, 16, 1087-1096.  
19833922 A.Liljas (2009).
Biochemistry. Leaps in translational elongation.
  Science, 326, 677-678.  
19144912 A.M.Giessing, S.S.Jensen, A.Rasmussen, L.H.Hansen, A.Gondela, K.Long, B.Vester, and F.Kirpekar (2009).
Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria.
  RNA, 15, 327-336.  
19929179 D.N.Wilson (2009).
The A-Z of bacterial translation inhibitors.
  Crit Rev Biochem Mol Biol, 44, 393-433.  
19702336 J.L.Miller, H.Cimen, H.Koc, and E.C.Koc (2009).
Phosphorylated proteins of the mammalian mitochondrial ribosome: implications in protein synthesis.
  J Proteome Res, 8, 4789-4798.  
19196969 L.C.Wieland Brown, M.G.Acker, J.Clardy, C.T.Walsh, and M.A.Fischbach (2009).
Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin.
  Proc Natl Acad Sci U S A, 106, 2549-2553.  
19369248 M.S.Dunstan, P.C.Hang, N.V.Zelinskaya, J.F.Honek, and G.L.Conn (2009).
Structure of the Thiostrepton Resistance Methyltransferase{middle dot}S-Adenosyl-L-methionine Complex and Its Interaction with Ribosomal RNA.
  J Biol Chem, 284, 17013-17020.
PDB code: 3gyq
19741022 M.de la Peña, D.Dufour, and J.Gallego (2009).
Three-way RNA junctions with remote tertiary contacts: a recurrent and highly versatile fold.
  RNA, 15, 1949-1964.  
19921000 S.Schoof, and H.D.Arndt (2009).
D-cysteine occurrence in thiostrepton may not necessitate an epimerase.
  Chem Commun (Camb), (), 7113-7115.  
19072817 S.Schoof, S.Baumann, B.Ellinger, and H.D.Arndt (2009).
A Fluorescent Probe for the 70 S-Ribosomal GTPase-Associated Center.
  Chembiochem, 10, 242-245.  
19838167 T.M.Schmeing, and V.Ramakrishnan (2009).
What recent ribosome structures have revealed about the mechanism of translation.
  Nature, 461, 1234-1242.  
19545171 X.Shi, K.Chiu, S.Ghosh, and S.Joseph (2009).
Bases in 16S rRNA important for subunit association, tRNA binding, and translocation.
  Biochemistry, 48, 6772-6782.  
19833919 Y.G.Gao, M.Selmer, C.M.Dunham, A.Weixlbaumer, A.C.Kelley, and V.Ramakrishnan (2009).
The structure of the ribosome with elongation factor G trapped in the posttranslocational state.
  Science, 326, 694-699.
PDB codes: 2wri 2wrj 2wrk 2wrl
18832371 A.Meskauskas, and J.D.Dinman (2008).
Ribosomal protein L3 functions as a 'rocker switch' to aid in coordinating of large subunit-associated functions in eukaryotes and Archaea.
  Nucleic Acids Res, 36, 6175-6186.  
18824477 A.N.Petrov, A.Meskauskas, S.C.Roshwalb, and J.D.Dinman (2008).
Yeast ribosomal protein L10 helps coordinate tRNA movement through the large subunit.
  Nucleic Acids Res, 36, 6187-6198.  
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.

 

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