scholarly journals Conformational characterization of full-length X-chromosome-linked inhibitor of apoptosis protein (XIAP) through an integrated approach

IUCrJ ◽  
2019 ◽  
Vol 6 (5) ◽  
pp. 948-957 ◽  
Author(s):  
Panagis Polykretis ◽  
Enrico Luchinat ◽  
Alessio Bonucci ◽  
Andrea Giachetti ◽  
Melissa A. Graewert ◽  
...  

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.

2007 ◽  
Vol 179 (1) ◽  
pp. 505-513 ◽  
Author(s):  
Alix Ashare ◽  
Martha M. Monick ◽  
Amanda B. Nymon ◽  
John M. Morrison ◽  
Matthew Noble ◽  
...  

Oncotarget ◽  
2015 ◽  
Vol 6 (6) ◽  
pp. 3784-3796 ◽  
Author(s):  
Chad M. McKee ◽  
Yunchuan Ding ◽  
Jianfeng Zhou ◽  
Chunrui Li ◽  
Liang Huang ◽  
...  

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