Elongation factor 1β of artemia: Localization of functional sites and homology to elongation factor 1δ

Damme, H.T.F. van; Amons, Reinout; Karssies, R.; Timmers, C.J.; Janssen, George M.C.; Möller, W.

doi:10.1016/0167-4781(90)90174-z

Cited by 92 publications

(52 citation statements)

References 23 publications

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“…47 In animals, eEF1 consists of four different subunits (eEF1A, eEF1BR, eEF1B , and eEF1Bγ, formerly collectively termed EF-1R γδ) that make up two functionally distinct parts; eEF1A‚GTP promotes the binding of aatRNA to the A-site of the ribosome under hydrolysis of GTP, whereas the heteromeric complexes eEF1BR‚ eEF1Bγ and eEF1BR‚eEF1Bγ‚eEF1B function by recycling the resulting inactive eEF1A‚GDP intermediate back to the active GTP-bound form by stimulating guanine nucleotide exchange on eEF1A (Figure 2). The highly homologous eEF1BR and eEF1B (Figure 8) display the same degree of exchange activity 48 but differ with respect to the mode and strength of their interaction with eEF1Bγ.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for the Binding of Didemnins to Human Elongation Factor eEF1A and Rationale for the Potent Antitumor Activity of These Marine Natural Products

et al. 2004

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Didemnins and tamandarins are closely related marine natural products with potent inhibitory effects on protein synthesis and cell viability. On the basis of available biochemical and structural evidence and results from molecular dynamics simulations, a model is proposed that accounts for the strong and selective binding of these compounds to human elongation factor eEF1A in the presence of GTP. We suggest that the p-methoxyphenyl ring of these cyclic depsipeptides is inserted into the same pocket in eEF1A that normally lodges either the 3′ terminal adenine of aminoacylated tRNA, as inferred from two prokaryotic EF-Tu‚GTP‚tRNA complexes, or the aromatic side chain of Phe/Tyr-163 from the nucleotide exchange factor eEF1BR, as observed in several X-ray crystal structures of a yeast eEF1A:eEF1BR complex. This pocket, which has a strong hydrophobic character, is formed by two protruding loops on the surface of eEF1A domain 2. Further stabilization of the bound depsipeptide is brought about by additional crucial interactions involving eEF1A domain 1 in such a way that the molecule fits snugly at the interface between these two domains. In the GDP-bound form of eEF1A, this binding site exists only as two separate halves, which accounts for the much greater affinity of didemnins for the GTP-bound form of this elongation factor. This binding mode is entirely different from those seen in the complexes of the homologous prokaryotic EF-Tu with kirromycin-type antibiotics or the cyclic thiazolyl peptide antibiotic GE2270A. Interestingly, the set of interactions used by didemnins to bind to eEF1A is also distinct from that used by eEF1BR or eEF1B , thus establishing a competition for binding to a common site that goes beyond simple molecular mimicry. The model presented here is consistent with both available biochemical evidence and known structure-activity relationships for these two classes of natural compounds and synthetic analogues and provides fertile ground for future research.

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Section: Discussionmentioning

confidence: 99%

Structural Basis for the Binding of Didemnins to Human Elongation Factor eEF1A and Rationale for the Potent Antitumor Activity of These Marine Natural Products

et al. 2004

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“…It has also been reported that EF-1␥ contains 2 internal repeats (VFGEXNXS) at amino acid residues 35-42 and 355-362. It is conceivable that the region of these two octapeptides of the EF-1␥ could be part of binding motif for EF-1␤ and EF-1␦, respectively, hence suggesting that EF-1␥ resides between the EF-1␤ and EF-1␦ in the complex (44,46). Since kinectin is an integral membrane protein on ER, it can interact with EF-1␦ and anchor the entire EF-1␤␥␦ complex onto ER.…”

Section: Discussionmentioning

confidence: 99%

Kinectin Anchors the Translation Elongation Factor-1δ to the Endoplasmic Reticulum

Ong

et al. 2003

Journal of Biological Chemistry

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Kinectin has been proposed to be a membrane anchor for kinesin on intracellular organelles. A kinectin isoform that lacks a major portion of the kinesin-binding domain does not bind kinesin but interacts with another resident of the endoplasmic reticulum, the translation elongation factor-1 delta (EF-1␦). This was shown by yeast two-hybrid analysis and a number of in vitro and in vivo assays. EF-1␦ provides the guanine nucleotide exchange activities on EF-1␣ during elongation step of protein synthesis. The minimal EF-1␦-binding domain on kinectin resides within a conserved region present in all the kinectin isoforms. Overexpression of the kinectin fragments in vivo disrupted the intracellular localization of EF-1␦ proteins. This report provides evidence of an alternative kinectin function as the membrane anchor for EF-1␦ on the endoplasmic reticulum and provides clues to the EF-1 complex assembly and anchorage on the endoplasmic reticulum.

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“…Using computer methods for database search, sequence motif analysis, multiple alignment, and tertiary structure modeling, we show here that the y subunit of eukaryotic translation elongation factor 1 (EFIy), which together with the / 3 and 6 subunits (EFlP and EF16) forms the guanine nucleotide exchange factor (Riis et al, 1990;Van Damme et al, 1990), contains an N-terminal GST-related domain. We propose that this domain may be involved in the regulation of the formation of multisubunit complexes containing EFI through the balance between disulfide bonds and free thiol groups of cysteines.…”

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confidence: 99%

Eukaryotic translation elongation factor 1γ contains a glutathione transferase domain—Study of a diverse, ancient protein super family using motif search and structural modeling

et al. 1994

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Using computer methods for multiple alignment, sequence motif search, and tertiary structure modeling, we show that eukaryotic translation elongation factor ly (EFly) contains an N-terminal domain related to class 0 glutathione S-transferases (GST). GST-like proteins related to class 8 comprise a large group including, in addition to typical GSTs and EFly, stress-induced proteins from bacteria and plants, bacterial reductive dehalogenases and P-etherases, and several uncharacterized proteins. These proteins share 2 conserved sequence motifs with GSTs of other classes (a, p, and K). Tertiary structure modeling showed that in spite of the relatively low sequence similarity, the GST-related domain of EFly is likely to form a fold very similar to that in the known structures of class a , p , and ?r GSTs. One of the conserved motifs is implicated in glutathione binding, whereas the other motif probably is involved in maintaining the proper conformation of the GST domain. We predict that the GSTlike domain in EFly is enzymatically active and that to exhibit GST activity, EFly has to form homodimers. The GST activity may be involved in the regulation of the assembly of multisubunit complexes containing EFl and aminoacyl-tRNA synthetases by shifting the balance between glutathione, disulfide glutathione, thiol groups of cysteines, and protein disulfide bonds. The GST domain is a widespread, conserved enzymatic module that may be covalently or noncovalently complexed with other proteins. Regulation of protein assembly and folding may be 1 of the functions of GST.

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Elongation factor 1β of artemia: Localization of functional sites and homology to elongation factor 1δ

Cited by 92 publications

References 23 publications

Structural Basis for the Binding of Didemnins to Human Elongation Factor eEF1A and Rationale for the Potent Antitumor Activity of These Marine Natural Products

Structural Basis for the Binding of Didemnins to Human Elongation Factor eEF1A and Rationale for the Potent Antitumor Activity of These Marine Natural Products

Kinectin Anchors the Translation Elongation Factor-1δ to the Endoplasmic Reticulum

Eukaryotic translation elongation factor 1γ contains a glutathione transferase domain—Study of a diverse, ancient protein super family using motif search and structural modeling

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