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PMID: 21051640 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The mechanism for activation of GTP hydrolysis on the ribosome.

Science (New York, N.Y.) ·Vol. 330 ·No. 6005 ·2010-11-05 ·Pages 835-838

Voorhees RM, Schmeing TM, Kelley AC, Ramakrishnan V

Abstract

Protein synthesis requires several guanosine triphosphatase (GTPase) factors, including elongation factor Tu (EF-Tu), which delivers aminoacyl-transfer RNAs (tRNAs) to the ribosome. To understand how the ribosome triggers GTP hydrolysis in translational GTPases, we have determined the crystal structure of EF-Tu and aminoacyl-tRNA bound to the ribosome with a GTP analog, to 3.2 angstrom resolution. EF-Tu is in its active conformation, the switch I loop is ordered, and the catalytic histidine is coordinating the nucleophilic water in position for inline attack on the γ-phosphate of GTP. This activated conformation is due to a critical and conserved interaction of the histidine with A2662 of the sarcin-ricin loop of the 23S ribosomal RNA. The structure suggests a universal mechanism for GTPase activation and hydrolysis in translational GTPases on the ribosome.

MeSH Terms
Bacterial Proteins/chemistry,metabolism Catalytic Domain Crystallography, X-Ray Enzyme Activation Guanosine Triphosphate/analogs & derivatives,metabolism Hydrolysis Hydrophobic and Hydrophilic Interactions Nucleic Acid Conformation Paromomycin/metabolism Peptide Elongation Factor Tu/chemistry,metabolism Phosphates/metabolism Protein Structure, Tertiary RNA, Bacterial/chemistry,metabolism RNA, Ribosomal, 23S/chemistry,metabolism RNA, Transfer, Amino Acyl/chemistry,metabolism Ribosomes/metabolism Thermus thermophilus/chemistry,metabolism,ultrastructure
Chemicals
Bacterial Proteins Phosphates RNA, Bacterial RNA, Ribosomal, 23S RNA, Transfer, Amino Acyl guanosine 5'-(beta,gamma-methylene)triphosphate Paromomycin Guanosine Triphosphate Peptide Elongation Factor Tu
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Voorhees Rebecca M
MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
Schmeing T Martin
MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
Kelley Ann C
MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
Ramakrishnan V
MRC Laboratory of Molecular Biology, Cambridge, UK, CB2 0QH.
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1194460
Published
2010-11-05
Pages
835-838
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3763471
Subset
IM
Grants
Wellcome Trust · 082086 · United Kingdom
Medical Research Council · MC_U105184332 · United Kingdom
Databases
PDB
2XQD, 2XQE
Corrections
CommentIn
PMID: 21719661
External Links
PubMed source DOI: 10.1126/science.1194460 PMC Full Text View journal details
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