دورية أكاديمية
A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation.
| العنوان: | A structural basis for IκB kinase 2 activation via oligomerization-dependent trans auto-phosphorylation. |
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| المؤلفون: | Smarajit Polley, De-Bin Huang, Arthur V Hauenstein, Amanda J Fusco, Xiangyang Zhong, Don Vu, Bärbel Schröfelbauer, Youngchang Kim, Alexander Hoffmann, Inder M Verma, Gourisankar Ghosh, Tom Huxford |
| المصدر: | PLoS Biology, Vol 11, Iss 6, p e1001581 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | Activation of the IκB kinase (IKK) is central to NF-κB signaling. However, the precise activation mechanism by which catalytic IKK subunits gain the ability to induce NF-κB transcriptional activity is not well understood. Here we report a 4 Å x-ray crystal structure of human IKK2 (hIKK2) in its catalytically active conformation. The hIKK2 domain architecture closely resembles that of Xenopus IKK2 (xIKK2). However, whereas inactivated xIKK2 displays a closed dimeric structure, hIKK2 dimers adopt open conformations that permit higher order oligomerization within the crystal. Reversible oligomerization of hIKK2 dimers is observed in solution. Mutagenesis confirms that two of the surfaces that mediate oligomerization within the crystal are also critical for the process of hIKK2 activation in cells. We propose that IKK2 dimers transiently associate with one another through these interaction surfaces to promote trans auto-phosphorylation as part of their mechanism of activation. This structure-based model supports recently published structural data that implicate strand exchange as part of a mechanism for IKK2 activation via trans auto-phosphorylation. Moreover, oligomerization through the interfaces identified in this study and subsequent trans auto-phosphorylation account for the rapid amplification of IKK2 phosphorylation observed even in the absence of any upstream kinase. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776406/?tool=EBITest; https://doaj.org/toc/1544-9173Test; https://doaj.org/toc/1545-7885Test |
| DOI: | 10.1371/journal.pbio.1001581 |
| الوصول الحر: | https://doaj.org/article/43e7e959d3ba4586a7f0c6da67fd6cc8Test |
| رقم الانضمام: | edsdoj.43e7e959d3ba4586a7f0c6da67fd6cc8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15449173 15457885 |
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| DOI: | 10.1371/journal.pbio.1001581 |