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Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach
The X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiatin...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760453/ https://www.ncbi.nlm.nih.gov/pubmed/31576227 http://dx.doi.org/10.1107/S205225251901073X |
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author | Polykretis, Panagis Luchinat, Enrico Bonucci, Alessio Giachetti, Andrea Graewert, Melissa A. Svergun, Dmitri I. Banci, Lucia |
author_facet | Polykretis, Panagis Luchinat, Enrico Bonucci, Alessio Giachetti, Andrea Graewert, Melissa A. Svergun, Dmitri I. Banci, Lucia |
author_sort | Polykretis, Panagis |
collection | PubMed |
description | The X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiating cell survival and resistance to chemotherapeutics, and has therefore become an important target for the treatment of malignancy. Despite the fact that the structure of each single domain is known, the conformation of the full-length protein has never been determined. Here, the first structural model of the full-length XIAP dimer, determined by an integrated approach using nuclear magnetic resonance, small-angle X-ray scattering and electron paramagnetic resonance data, is presented. It is shown that XIAP adopts a compact and relatively rigid conformation, implying that the spatial arrangement of its domains must be taken into account when studying the interactions with its physiological partners and in developing effective inhibitors. |
format | Online Article Text |
id | pubmed-6760453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-67604532019-10-01 Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach Polykretis, Panagis Luchinat, Enrico Bonucci, Alessio Giachetti, Andrea Graewert, Melissa A. Svergun, Dmitri I. Banci, Lucia IUCrJ Research Papers The X-chromosome-linked inhibitor of apoptosis protein (XIAP) is a multidomain protein whose main function is to block apoptosis by caspase inhibition. XIAP is also involved in other signalling pathways, including NF-κB activation and copper homeostasis. XIAP is overexpressed in tumours, potentiating cell survival and resistance to chemotherapeutics, and has therefore become an important target for the treatment of malignancy. Despite the fact that the structure of each single domain is known, the conformation of the full-length protein has never been determined. Here, the first structural model of the full-length XIAP dimer, determined by an integrated approach using nuclear magnetic resonance, small-angle X-ray scattering and electron paramagnetic resonance data, is presented. It is shown that XIAP adopts a compact and relatively rigid conformation, implying that the spatial arrangement of its domains must be taken into account when studying the interactions with its physiological partners and in developing effective inhibitors. International Union of Crystallography 2019-08-23 /pmc/articles/PMC6760453/ /pubmed/31576227 http://dx.doi.org/10.1107/S205225251901073X Text en © Panagis Polykretis et al. 2019 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Research Papers Polykretis, Panagis Luchinat, Enrico Bonucci, Alessio Giachetti, Andrea Graewert, Melissa A. Svergun, Dmitri I. Banci, Lucia Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title | Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title_full | Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title_fullStr | Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title_full_unstemmed | Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title_short | Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach |
title_sort | conformational characterization of full-length x-chromosome-linked inhibitor of apoptosis protein (xiap) through an integrated approach |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760453/ https://www.ncbi.nlm.nih.gov/pubmed/31576227 http://dx.doi.org/10.1107/S205225251901073X |
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