4DNI

Structure of Editosome protein

Summary for 4DNI

• Entry DOI: 10.2210/pdb4dni/pdb
• Descriptor: Fusion protein of RNA-editing complex proteins MP42 and MP18 (2 entities in total)
• Functional Keywords: krepa3, krepa6, editosome, protein/rna binding, protein binding, rna binding protein
• Biological source: Trypanosoma brucei; More
• Total number of polymer chains: 1
• Total formula weight: 28866.66

Authors

Park, Y.-J.,Hol, W. (deposition date: 2012-02-08, release date: 2012-12-26, Last modification date: 2024-02-28)

Primary citation

Park, Y.J.,Hol, W.G.
Explorations of linked editosome domains leading to the discovery of motifs defining conserved pockets in editosome OB-folds.
J.Struct.Biol., 180:362-373, 2012

PubMed Abstract: Trypanosomatids form a group of protozoa which contain parasites of human, animals and plants. Several of these species cause major human diseases, including Trypanosoma brucei which is the causative agent of human African trypanosomiasis, also called sleeping sickness. These organisms have many highly unusual features including a unique U-insertion/deletion RNA editing process in the single mitochondrion. A key multi-protein complex, called the ∼20S editosome, or editosome, carries out a cascade of essential RNA-modifying reactions and contains a core of 12 different proteins of which six are the interaction proteins A1 to A6. Each of these interaction proteins comprises a C-terminal OB-fold and the smallest interaction protein A6 has been shown to interact with four other editosome OB-folds. Here we report the results of a "linked OB-fold" approach to obtain a view of how multiple OB-folds might interact in the core of the editosome. Constructs with variants of linked domains in 25 expression and co-expression experiments resulted in 13 soluble multi-OB-fold complexes. In several instances, these complexes were more homogeneous in size than those obtained from corresponding unlinked OB-folds. The crystal structure of A3(OB) linked to A6 could be elucidated and confirmed the tight interaction between these two OB domains as seen also in our recent complex of A3(OB) and A6 with nanobodies. In the current crystal structure of A3(OB) linked to A6, hydrophobic side chains reside in well-defined pockets of neighboring OB-fold domains. When analyzing the available crystal structures of editosome OB-folds, it appears that in five instances "Pocket 1" of A1(OB), A3(OB) and A6 is occupied by a hydrophobic side chain from a neighboring protein. In these three different OB-folds, Pocket 1 is formed by two conserved sequence motifs and an invariant arginine. These pockets might play a key role in the assembly or mechanism of the editosome by interacting with hydrophobic side chains from other proteins.

PubMed: 22902563
DOI: 10.1016/j.jsb.2012.07.012

Experimental method

X-RAY DIFFRACTION (2.55 Å)