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Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287191/ https://www.ncbi.nlm.nih.gov/pubmed/22039098 http://dx.doi.org/10.1093/nar/gkr867 |
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author | Park, Young-Jun Pardon, Els Wu, Meiting Steyaert, Jan Hol, Wim G. J. |
author_facet | Park, Young-Jun Pardon, Els Wu, Meiting Steyaert, Jan Hol, Wim G. J. |
author_sort | Park, Young-Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3287191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32871912012-02-27 Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody Park, Young-Jun Pardon, Els Wu, Meiting Steyaert, Jan Hol, Wim G. J. Nucleic Acids Res Structural Biology 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. Oxford University Press 2012-02 2011-10-27 /pmc/articles/PMC3287191/ /pubmed/22039098 http://dx.doi.org/10.1093/nar/gkr867 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Structural Biology Park, Young-Jun Pardon, Els Wu, Meiting Steyaert, Jan Hol, Wim G. J. Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title | Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title_full | Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title_fullStr | Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title_full_unstemmed | Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title_short | Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
title_sort | crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3287191/ https://www.ncbi.nlm.nih.gov/pubmed/22039098 http://dx.doi.org/10.1093/nar/gkr867 |
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