The Human SepSecS-tRNASec Complex Reveals the Mechanism of Selenocysteine Formation
Sotiria Palioura,1
R. Lynn Sherrer,1
Thomas A. Steitz,1,2,3
Dieter Söll,1,2,*
Miljan Simonovi
4,*
Selenocysteine is the only genetically encoded amino acid in
humans whose biosynthesis occurs on its cognate transfer RNA
(tRNA).
O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS)
catalyzes the final step of selenocysteine formation by a poorly
understood tRNA-dependent mechanism. The crystal structure of
human tRNA
Sec in complex with SepSecS, phosphoserine, and thiophosphate,
together with in vivo and in vitro enzyme assays, supports a
pyridoxal phosphate–dependent mechanism of Sec-tRNA
Sec formation. Two tRNA
Sec molecules, with a fold distinct from
other canonical tRNAs, bind to each SepSecS tetramer through
their 13–base pair acceptor-T
C arm (where
indicates pseudouridine).
The tRNA binding is likely to induce a conformational change
in the enzyme’s active site that allows a phosphoserine
covalently attached to tRNA
Sec, but not free phosphoserine,
to be oriented properly for the reaction to occur.
2 Department of Chemistry, Yale University, New Haven, CT 06520, USA.
3 Howard Hughes Medical Institute, Yale University, New Haven, CT06520, USA.
4 Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
* To whom correspondence should be addressed. E-mail: dieter.soll{at}yale.edu (D.S.); }{msimon5{at}uic.edu}{ (M.S.)
