Details

Autor(en) / Beteiligte

• Kolaj‐Robin, Olga
• McEwen, Alastair G
• Cavarelli, Jean
• Séraphin, Bertrand

Titel

Structure of the Elongator cofactor complex Kti11/Kti13 provides insight into the role of Kti13 in Elongator‐dependent tRNA modification

Ist Teil von

• The FEBS journal, 2015-03, Vol.282 (5), p.819-833

Ort / Verlag

England: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies

Erscheinungsjahr

2015

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Modification of wobble uridines of many eukaryotic tRNAs requires the Elongator complex, a highly conserved six‐subunit eukaryotic protein assembly, as well as the Killer toxin‐insensitive (Kti) proteins 11–14. Kti11 was additionally shown to be implicated in the biosynthesis of diphthamide, a post‐translationally modified histidine of translation elongation factor 2. Recent data indicate that iron‐bearing Kti11 functions as an electron donor to the [4Fe–4S] cluster of radical S‐Adenosylmethionine enzymes, triggering the subsequent radical reaction. We show here that recombinant yeast Kti11 forms a stable 1 : 1 complex with Kti13. To obtain insights into the function of this heterodimer, the Kti11/Kti13 complex was purified to homogeneity, crystallized, and its structure determined at 1.45 Å resolution. The importance of several residues mediating complex formation was confirmed by mutagenesis. Kti13 adopts a fold characteristic of RCC1‐like proteins. The seven‐bladed β‐propeller consists of a unique mixture of four‐ and three‐stranded blades. In the complex, Kti13 orients Kti11 and restricts access to its electron‐carrying iron atom, constraining the electron transfer capacity of Kti11. Based on these findings, we propose a role for Kti13, and discuss the possible functional implications of complex formation. DATABASE: Structural data have been submitted to the Protein Data Bank under accession number 4X33.