Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach.
EPR
SAXS
X-chromosome-linked inhibitor of apoptosis protein
full-length XIAP
integrative structural biology
Journal
IUCrJ
ISSN: 2052-2525
Titre abrégé: IUCrJ
Pays: England
ID NLM: 101623101
Informations de publication
Date de publication:
01 Sep 2019
01 Sep 2019
Historique:
received:
09
04
2019
accepted:
31
07
2019
entrez:
3
10
2019
pubmed:
3
10
2019
medline:
3
10
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31576227
doi: 10.1107/S205225251901073X
pii: lz5027
pmc: PMC6760453
doi:
Types de publication
Journal Article
Langues
eng
Pagination
948-957Informations de copyright
© Panagis Polykretis et al. 2019.
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