Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis

French, Rachel L.; Gupta, Nakul; Copeland, Paul R.; Simonović, Miljan

doi:10.1074/jbc.m114.597955

Cited by 13 publications

(21 citation statements)

References 48 publications

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“…Until detailed studies are performed that establish the in vivo ratios of all of the factors, it will not be possible to sort out whether eEF1A must be actively prevented from Sec-tRNA Sec binding or whether there simply is never an opportunity for binding due to the stoichiometry of factors. Along those lines, a recent study shows that the endogenous SepSecS enzyme that converts Ser to Sec after serine phosphorylation is present as a more than 3-fold molar excess over total tRNA Sec in human hepatoma cells, thus supporting the idea that Sec-tRNA Sec may be “channeled” onto eEFSec by virtue of its complex synthetic pathway (French et al, 2014). …”

Section: 2 Elongation Factor Specificitymentioning

confidence: 82%

Selenocysteine incorporation: A trump card in the game of mRNA decay

Shetty

Copeland

2015

Biochimie

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The incorporation of the 21st amino acid, selenocysteine (Sec), occurs on mRNAs that harbor in-frame stop codons because the Sec-tRNASec recognizes a UGA codon. This sets up an intriguing interplay between translation elongation, translation termination and the complex machinery that marks mRNAs that contain premature termination codons for degradation, leading to nonsense mediated mRNA decay (NMD). In this review we discuss the intricate and complex relationship between this key quality control mechanism and the process of Sec incorporation in mammals.

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Section: 2 Elongation Factor Specificitymentioning

confidence: 82%

Selenocysteine incorporation: A trump card in the game of mRNA decay

Shetty

Copeland

2015

Biochimie

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“…Recently, French et al . have shown that the SepSecS tetramer is able to bind to one or two tRNA Sec molecules ( 45 ), but the binding preference of hSerRS to tRNA Sec is not clear. In this study, we obtained two types of complexes of crystals in different stoichiometry to rule out the possibility of crystallization artifacts.…”

Section: Discussionmentioning

confidence: 99%

SerRS-tRNA^Seccomplex structures reveal mechanism of the first step in selenocysteine biosynthesis

et al. 2015

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Selenocysteine (Sec) is found in the catalytic centers of many selenoproteins and plays important roles in living organisms. Malfunctions of selenoproteins lead to various human disorders including cancer. Known as the 21st amino acid, the biosynthesis of Sec involves unusual pathways consisting of several stages. While the later stages of the pathways are well elucidated, the molecular basis of the first stage—the serylation of Sec-specific tRNA (tRNASec) catalyzed by seryl-tRNA synthetase (SerRS)—is unclear. Here we present two cocrystal structures of human SerRS bound with tRNASec in different stoichiometry and confirm the formation of both complexes in solution by various characterization techniques. We discovered that the enzyme mainly recognizes the backbone of the long variable arm of tRNASec with few base-specific contacts. The N-terminal coiled-coil region works like a long-range lever to precisely direct tRNA 3′ end to the other protein subunit for aminoacylation in a conformation-dependent manner. Restraints of the flexibility of the coiled-coil greatly reduce serylation efficiencies. Lastly, modeling studies suggest that the local differences present in the D- and T-regions as well as the characteristic U20:G19:C56 base triple in tRNASec may allow SerRS to distinguish tRNASec from closely related tRNASer substrate.

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“…In order to examine whether the solution conformation and interactions of SepSecS with tRNA Sec parallel those observed in the high-resolution structure, French and co-workers [54] performed a series of sedimentation velocity, SEC-MALLS (size exclusion chromatography coupled with multiangle laser light scattering) and SAXS (small angle X-ray scattering)…”

Section: The Terminal Catalytic Complex In Selenocysteine Synthesismentioning

confidence: 99%

Analytical ultracentrifugation: A versatile tool for the characterisation of macromolecular complexes in solution

Patel

Winzor

Scott

2016

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Analytical ultracentrifugation, an early technique developed for characterizing quantitatively the solution properties of macromolecules, remains a powerful aid to structural biologists in their quest to understand the formation of biologically important protein complexes at the molecular level. Treatment of the basic tenets of the sedimentation velocity and sedimentation equilibrium variants of analytical ultracentrifugation is followed by considerations of the roles that it, in conjunction with other physicochemical procedures, has played in resolving problems encountered in the delineation of complex formation for three biological systems - the cytoplasmic dynein complex, mitogen-activated protein kinase (ERK2) self-interaction, and the terminal catalytic complex in selenocysteine synthesis.

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Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis

Cited by 13 publications

References 48 publications

Selenocysteine incorporation: A trump card in the game of mRNA decay

Selenocysteine incorporation: A trump card in the game of mRNA decay

SerRS-tRNA^Seccomplex structures reveal mechanism of the first step in selenocysteine biosynthesis

Analytical ultracentrifugation: A versatile tool for the characterisation of macromolecular complexes in solution

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Structural Asymmetry of the Terminal Catalytic Complex in Selenocysteine Synthesis

Cited by 13 publications

References 48 publications

Selenocysteine incorporation: A trump card in the game of mRNA decay

Selenocysteine incorporation: A trump card in the game of mRNA decay

SerRS-tRNASeccomplex structures reveal mechanism of the first step in selenocysteine biosynthesis

Analytical ultracentrifugation: A versatile tool for the characterisation of macromolecular complexes in solution

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Product

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SerRS-tRNA^Seccomplex structures reveal mechanism of the first step in selenocysteine biosynthesis