Structural basis of the ribosomal machinery for peptide bond formation, translocation, and nascent chain progression.
Crystal structures of tRNA mimics complexed with the large ribosomal subunit of Deinococcus radiodurans indicate that remote interactions determine the precise orientation of tRNA in the peptidyl-transferase center (PTC). The PTC tolerates various orientations of puromycin derivatives and its flexibility allows the conformational rearrangements required for peptide-bond formation. Sparsomycin binds to A2602 and alters the PTC conformation. H69, the intersubunit-bridge connecting the PTC and decoding site, may also participate in tRNA placement and translocation. A spiral rotation of the 3' end of the A-site tRNA around a 2-fold axis of symmetry identified within the PTC suggests a unified ribosomal machinery for peptide-bond formation, A-to-P-site translocation, and entrance of nascent proteins into the exit tunnel. Similar 2-fold related regions, detected in all known structures of large ribosomal subunits, indicate the universality of this mechanism.
Bashan
Anat
A
Department of Structural Biology, Weizmann Institute, 76100 Rehovot, Israel.
Agmon
Ilana
I
Zarivach
Raz
R
Schluenzen
Frank
F
Harms
Joerg
J
Berisio
Rita
R
Bartels
Heike
H
Franceschi
Francois
F
Auerbach
Tamar
T
Hansen
Harly A S
HA
Kossoy
Elizaveta
E
Kessler
Maggie
M
Yonath
Ada
A
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D034301:Deinococcus / Q000235:genetics*; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism; D011691:Puromycin / Q000737:chemistry / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013033:Sparsomycin / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D011500:Protein Synthesis Inhibitors; D012346:RNA, Transfer, Amino Acyl; D012269:Ribosomal Proteins; D011691:Puromycin; D013033:Sparsomycin