دورية أكاديمية
أعرض في EDS

A conformational switch regulates the ubiquitin ligase HUWE1

التفاصيل البيبلوغرافية
العنوان: A conformational switch regulates the ubiquitin ligase HUWE1
المؤلفون: Bodo Sander, Wenshan Xu, Martin Eilers, Nikita Popov, Sonja Lorenz
المصدر: eLife, Vol 6 (2017)
بيانات النشر: eLife Sciences Publications Ltd, 2017.
سنة النشر: 2017
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: HUWE1, HECT ligase, ubiquitin, p14ARF, X-ray crystallography, enzyme regulation, Medicine, Science, Biology (General), QH301-705.5
الوصف: The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
العلاقة: https://elifesciences.org/articles/21036Test; https://doaj.org/toc/2050-084XTest
DOI: 10.7554/eLife.21036
الوصول الحر: https://doaj.org/article/915107bca11b4a89909e073ac8129672Test
رقم الانضمام: edsdoj.915107bca11b4a89909e073ac8129672
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.21036