Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases.
Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases.
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DOI：
10.1016/j.molcel.2012.07.001
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发表时间：
2012-09-28
期刊：
影响因子：
16
通讯作者：
Klevit, Rachel E.
中科院分区：
文献类型：
--
作者：
Pruneda, Jonathan N.;Littlefield, Peter J.;Soss, Sarah E.;Nordquist, Kyle A.;Chazin, Walter J.;Brzovic, Peter S.;Klevit, Rachel E.
Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanism by which this class of enzymes facilitates Ub transfer remains enigmatic. Here we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 sidechain and an E2 backbone carbonyl, observed in all structures of active RING/U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformational biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/U-Box activation of E2~Ub conjugates.
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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