8g9z

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High-resolution crystal structure of the human selenomethionine-derived SepSecS-tRNASec complex

Structural highlights

8g9z is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.07Å
Ligands:MPD, MSE, PLR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPCS_HUMAN

Publication Abstract from PubMed

O-Phosphoseryl-tRNASec selenium transferase (SepSecS) catalyzes the terminal step of selenocysteine (Sec) synthesis in archaea and eukaryotes. How the Sec synthetic machinery recognizes and discriminates tRNASec from the tRNA pool is essential to the integrity of the selenoproteome. Previously, we suggested that SepSecS adopts a competent conformation that is pre-ordered for catalysis. Herein, using high-resolution X-ray crystallography, we visualized tRNA-dependent conformational changes in human SepSecS that may be a prerequisite for achieving catalytic competency. We show that tRNASec binding organizes the active sites of the catalytic protomer, while stabilizing the N- and C-termini of the non-catalytic protomer. Binding of large anions to the catalytic groove may further optimize the catalytic site for substrate binding and catalysis. Our biochemical and mutational analyses demonstrate that productive SepSecS*tRNASec complex formation is enthalpically driven and primarily governed by electrostatic interactions between the acceptor-, TPsiC-, and variable arms of tRNASec and helices alpha1 and alpha14 of SepSecS. The detailed visualization of the tRNA-dependent activation of SepSecS provides a structural basis for a revised model of the terminal reaction of Sec formation in archaea and eukaryotes.

Structural basis for the tRNA-dependent activation of the terminal complex of selenocysteine synthesis in humans.,Puppala AK, Castillo Suchkou J, French RL, Kiernan KA, Simonovic M Nucleic Acids Res. 2023 May 8;51(8):4012-4026. doi: 10.1093/nar/gkad182. PMID:36929010[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Puppala AK, Castillo Suchkou J, French RL, Kiernan KA, Simonović M. Structural basis for the tRNA-dependent activation of the terminal complex of selenocysteine synthesis in humans. Nucleic Acids Res. 2023 Mar 17:gkad182. PMID:36929010 doi:10.1093/nar/gkad182

Contents


PDB ID 8g9z

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