کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2035034 1072125 2016 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C
چکیده انگلیسی


• Cryo-EM shows mechanisms of polyubiquitination by cell-cycle regulator APC/C
• Distinct cullin-RING-E2 architectures for multiubiquitination and chain elongation
• RING activates UBE2C and binds substrate-linked ubiquitin to amplify processivity
• RING delivers ubiquitin for K11-linked chain elongation by UBE2S placed by cullin

SummaryProtein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3–E2–substrate-UB architectures control different forms of polyubiquitination.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 165, Issue 6, 2 June 2016, Pages 1440–1453
نویسندگان
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