PMID- 10368288
OWN - NLM
STAT- MEDLINE
DCOM- 19990329
LR  - 20170804
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 2
DP  - 1999 Feb 15
TI  - The solution structure of the guanine nucleotide exchange domain of human
      elongation factor 1beta reveals a striking resemblance to that of EF-Ts from
      Escherichia coli.
PG  - 217-26
AB  - BACKGROUND: In eukaryotic protein synthesis, the multi-subunit elongation factor 
      1 (EF-1) plays an important role in ensuring the fidelity and regulating the rate
      of translation. EF-1alpha, which transports the aminoacyl tRNA to the ribosome,
      is a member of the G-protein superfamily. EF-1beta regulates the activity of
      EF-1alpha by catalyzing the exchange of GDP for GTP and thereby regenerating the 
      active form of EF-1alpha. The structure of the bacterial analog of EF-1alpha,
      EF-Tu has been solved in complex with its GDP exchange factor, EF-Ts. These
      structures indicate a mechanism for GDP-GTP exchange in prokaryotes. Although
      there is good sequence conservation between EF-1alpha and EF-Tu, there is
      essentially no sequence similarity between EF-1beta and EF-Ts. We wished to
      explore whether the prokaryotic exchange mechanism could shed any light on the
      mechanism of eukaryotic translation elongation. RESULTS: Here, we report the
      structure of the guanine-nucleotide exchange factor (GEF) domain of human
      EF-1beta (hEF-1beta, residues 135-224); hEF-1beta[135-224], determined by nuclear
      magnetic resonance spectroscopy. Sequence conservation analysis of the GEF
      domains of EF-1 subunits beta and delta from widely divergent organisms indicates
      that the most highly conserved residues are in two loop regions. Intriguingly,
      hEF-1beta[135-224] shares structural homology with the GEF domain of EF-Ts
      despite their different primary sequences. CONCLUSIONS: On the basis of both the 
      structural homology between EF-Ts and hEF-1beta[135-224] and the sequence
      conservation analysis, we propose that the mechanism of guanine-nucleotide
      exchange in protein synthesis has been conserved in prokaryotes and eukaryotes.
      In particular, Tyr181 of hEF-1beta[135-224] appears to be analogous to Phe81 of
      Escherichia coli EF-Ts.
FAU - Perez, J M
AU  - Perez JM
AD  - Department of Molecular Cell Biology, Sylvius Laboratory, University ofLeiden,
      Wassenaarseweg 72 NL-2333, AL Leiden, The Netherlands.
FAU - Siegal, G
AU  - Siegal G
FAU - Kriek, J
AU  - Kriek J
FAU - Hard, K
AU  - Hard K
FAU - Dijk, J
AU  - Dijk J
FAU - Canters, G W
AU  - Canters GW
FAU - Moller, W
AU  - Moller W
LA  - eng
SI  - PDB/1B64
PT  - Journal Article
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Peptide Elongation Factor 1)
RN  - 0 (Peptide Elongation Factors)
RN  - 0 (Proteins)
RN  - 0 (elongation factor Ts)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Conserved Sequence/genetics
MH  - Escherichia coli/*metabolism
MH  - Eukaryotic Cells/metabolism
MH  - Guanine Nucleotide Exchange Factors
MH  - Guanosine Diphosphate/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Magnetic Resonance Spectroscopy
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Peptide Elongation Factor 1
MH  - Peptide Elongation Factors/*chemistry
MH  - Prokaryotic Cells/metabolism
MH  - Protein Biosynthesis/genetics
MH  - Protein Structure, Secondary
MH  - Proteins/*chemistry
MH  - Sequence Alignment
EDAT- 1999/06/16 00:00
MHDA- 1999/06/16 00:01
CRDT- 1999/06/16 00:00
PHST- 1999/06/16 00:00 [pubmed]
PHST- 1999/06/16 00:01 [medline]
PHST- 1999/06/16 00:00 [entrez]
AID - S0969-2126(99)80027-6 [pii]
PST - ppublish
SO  - Structure. 1999 Feb 15;7(2):217-26.