Report

Decameric SelA•tRNASec Ring Structure Reveals Mechanism of Bacterial Selenocysteine Formation

+ See all authors and affiliations

Science  05 Apr 2013:
Vol. 340, Issue 6128, pp. 75-78
DOI: 10.1126/science.1229521

You are currently viewing the abstract.

View Full Text

Putting Selenium in Proteins

The 21st amino acid, selenocysteine (Sec), occurs in the active site of many redox enzymes. Its cognate transfer RNA (tRNA) is first loaded with Ser by seryl-tRNA synthetase and the Ser-tRNASec is then converted to Sec-tRNASec. Itoh et al. (p. 75) determined the crystal structures of the selenocysteine synthase, SelA, that is responsible for this conversion in bacteria, alone and in complex with tRNA. The decameric SelA complex binds to 10 tRNASec molecules. The structures, together with biochemistry, show how SelA discriminates tRNASec from tRNASer, give insight into the mechanism of catalysis, and show that decamerization is essential for function.

Abstract

The 21st amino acid, selenocysteine (Sec), is synthesized on its cognate transfer RNA (tRNASec). In bacteria, SelA synthesizes Sec from Ser-tRNASec, whereas in archaea and eukaryotes SepSecS forms Sec from phosphoserine (Sep) acylated to tRNASec. We determined the crystal structures of Aquifex aeolicus SelA complexes, which revealed a ring-shaped homodecamer that binds 10 tRNASec molecules, each interacting with four SelA subunits. The SelA N-terminal domain binds the tRNASec-specific D-arm structure, thereby discriminating Ser-tRNASec from Ser-tRNASer. A large cleft is created between two subunits and accommodates the 3′-terminal region of Ser-tRNASec. The SelA structures together with in vivo and in vitro enzyme assays show decamerization to be essential for SelA function. SelA catalyzes pyridoxal 5′-phosphate–dependent Sec formation involving Arg residues nonhomologous to those in SepSecS. Different protein architecture and substrate coordination of the bacterial enzyme provide structural evidence for independent evolution of the two Sec synthesis systems present in nature.

View Full Text