3STB

A complex of two editosome proteins and two nanobodies

Summary for 3STB

• Entry DOI: 10.2210/pdb3stb/pdb
• Descriptor: single domain antibody VHH, RNA-editing complex protein MP42, MP18 RNA editing complex protein, ... (4 entities in total)
• Functional Keywords: rna editing, editosome, nanobody, single domain antibody, vhh, krepa3, krepa6, rna binding protein-immune system complex, rna binding protein/immune system
• Biological source: Lama glama; More
• Total number of polymer chains: 4
• Total formula weight: 61274.44

Authors

Park, Y.-J.,Hol, W. (deposition date: 2011-07-09, release date: 2011-11-02, Last modification date: 2024-11-20)

Primary citation

Park, Y.J.,Pardon, E.,Wu, M.,Steyaert, J.,Hol, W.G.
Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody.
Nucleic Acids Res., 40:1828-1840, 2012

PubMed Abstract: The parasite Trypanosoma brucei, the causative agent of sleeping sickness across sub-Saharan Africa, depends on a remarkable U-insertion/deletion RNA editing process in its mitochondrion. A approximately 20 S multi-protein complex, called the editosome, is an essential machinery for editing pre-mRNA molecules encoding the majority of mitochondrial proteins. Editosomes contain a common core of twelve proteins where six OB-fold interaction proteins, called A1-A6, play a crucial role. Here, we report the structure of two single-strand nucleic acid-binding OB-folds from interaction proteins A3 and A6 that surprisingly, form a heterodimer. Crystal growth required the assistance of an anti-A3 nanobody as a crystallization chaperone. Unexpectedly, this anti-A3 nanobody binds to both A3(OB) and A6, despite only ~40% amino acid sequence identity between the OB-folds of A3 and A6. The A3(OB)-A6 heterodimer buries 35% more surface area than the A6 homodimer. This is attributed mainly to the presence of a conserved Pro-rich loop in A3(OB). The implications of the A3(OB)-A6 heterodimer, and of a dimer of heterodimers observed in the crystals, for the architecture of the editosome are profound, resulting in a proposal of a 'five OB-fold center' in the core of the editosome.

PubMed: 22039098
DOI: 10.1093/nar/gkr867

Experimental method

X-RAY DIFFRACTION (2.5 Å)