PDBsum entry 3cc2

Ribosome

PDB id: 3cc2

Contents

Protein chains

237 a.a.

337 a.a.

246 a.a.

140 a.a.

172 a.a.

119 a.a.

29 a.a.

160 a.a.

70 a.a.

142 a.a.

132 a.a.

145 a.a.

194 a.a.

186 a.a.

115 a.a.

143 a.a.

95 a.a.

150 a.a.

81 a.a.

119 a.a.

53 a.a.

65 a.a.

154 a.a.

82 a.a.

142 a.a.

73 a.a.

56 a.a.

46 a.a.

92 a.a.

DNA/RNA

Metals

_CL ×22

_NA ×86

_MG ×116

_CD ×5

__K ×2

Waters ×7823

References listed in PDB file

Key reference

Title

Mutations outside the anisomycin-Binding site can make ribosomes drug-Resistant.

Authors

G.Blaha, G.Gürel, S.J.Schroeder, P.B.Moore, T.A.Steitz.

Ref.

J Mol Biol, 2008, 379, 505-519. [DOI no: 10.1016/j.jmb.2008.03.075]

PubMed id

18455733

Abstract

Eleven mutations that make Haloarcula marismortui resistant to anisomycin, an antibiotic that competes with the amino acid side chains of aminoacyl tRNAs for binding to the A-site cleft of the large ribosomal unit, have been identified in 23S rRNA. The correlation observed between the sensitivity of H. marismortui to anisomycin and the affinity of its large ribosomal subunits for the drug indicates that its response to anisomycin is determined primarily by the binding of the drug to its large ribosomal subunit. The structures of large ribosomal subunits containing resistance mutations show that these mutations can be divided into two classes: (1) those that interfere with specific drug-ribosome interactions and (2) those that stabilize the apo conformation of the A-site cleft of the ribosome relative to its drug-bound conformation. The conformational effects of some mutations of the second kind propagate through the ribosome for considerable distances and are reversed when A-site substrates bind to the ribosome.

Figure 2.
Fig. 2. A global view of the positions of the bases, the mutation of which cause anisomycin resistance in H. marismortui. The drug (gold with spherical atoms) is shown surrounded by the bases, the mutation of which leads to drug resistance (red). The backbone connecting the bases is indicated in gray. The positions occupied by the CCA end of P-site-bound tRNA (orange) and A-site-bound tRNA (green) are shown for orientation. E. coli numbering is used for all bases.

Figure 5.
Fig. 5. The effect of A-site substrate binding on the conformation of large ribosomal subunits containing the mutation G2581A. (a) Comparison of the conformation of the 2581 region of wild-type ribosomes (gray) with that of the G2581A mutant (green). Also included in the figure is CC-puromycin (blue green) as reference for the binding site of amino acylated tRNA to the A-site. (b) Comparison of the structure of G2581A mutant (green) and CC-puromycin bound to a large ribosomal subunit of wild type (gold). (c) Comparison of the structures of G2581A mutant (green) and of CC-puromycin bound to G2581A (khaki) with overlaid (F[G2581A]−F[G2581A CC-puromycin]) difference electron density, which was computed by using as amplitudes the differences observed between the data obtained from G2581A crystals that include the analog and the data obtained from G2581A crystals that lack the analog. Positive features were contoured at + 4σ (blue), and negative features were contoured at − 4σ (red).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 379, 505-519) copyright 2008.

Secondary reference #1

Title

The roles of ribosomal proteins in the structure assembly, And evolution of the large ribosomal subunit.

Authors

D.J.Klein, P.B.Moore, T.A.Steitz.

Ref.

J Mol Biol, 2004, 340, 141-177. [DOI no: 10.1016/j.jmb.2004.03.076]

PubMed id

15184028

Figure 12.
Figure 12. Comparison of L15 and L18e. (a) Ribbon representation of residues 65-164 of L15 (green) superimposed on L18e (red). Residues 83-89 in L15 are disordered and account for the break (*) in the L15 chain. (b) Stereo-view showing atomic details of the L18e (red)-RNA (blue) interaction. L65 lies in the hydrophobic core of this interface with specificity imparted by N44 and K63 hydrogen bonding (broken lines). (c) The L15 (green) interaction with RNA (blue) is shown in the same orientation as (b). The binding site in RNA is made up of identical nucleotides, except for G697. Lys107, Val108, Leu109, and F125 are identical with the corresponding residues in L18e. Structural homology was identified using DALI[83.] and models were superimposed using O. [76.]

Figure 18.
Figure 18. Absentee proteins in the H. marismortui and D. radiodurans ribosomes. (a) The L18e protein and its binding site in the H. marismortui 23 S RNA is shown with the corresponding region of the D. radiodurans 23 S RNA that lacks a protein. (b) The N-terminal domain of L19e from H. marismortui and the equivalent region of the D. radiodurans ribosome where H59 partially substitutes for the L19e protein. (c) The region of H. marismortui 23 S RNA that lacks any protein and the corresponding region of the D. radiodurans structure that contains L36.

The above figures are reproduced from the cited reference with permission from Elsevier

Secondary reference #2

Title

Genome sequence of haloarcula marismortui: a halophilic archaeon from the dead sea.

Authors

N.S.Baliga, R.Bonneau, M.T.Facciotti, M.Pan, G.Glusman, E.W.Deutsch, P.Shannon, Y.Chiu, R.S.Weng, R.R.Gan, P.Hung, S.V.Date, E.Marcotte, L.Hood, W.V.Ng.

Ref.

Genome Res, 2004, 14, 2221-2234.

PubMed id

15520287