Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
- Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, China
- Zhejiang University School of Medicine, China
Abstract
A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, a polyubiquitin is found in different arrangements of ubiquitin subunits. To understand the structural basis for polyubiquitin quaternary plasticity and to explore the target recognition mechanism, we characterize the conformational space of Lys63-linked diubiquitin (K63-Ub2). Refining against inter-subunit paramagnetic NMR data, we show that free K63-Ub2 exists as a dynamic ensemble comprising multiple closed and open quaternary states. The quaternary dynamics enables K63-Ub2 to be specifically recognized in a variety of signaling pathways. When binding to a target protein, one of the preexisting quaternary states is selected and stabilized. A point mutation that shifts the equilibrium between the different states modulates the binding affinities towards K63-Ub2 ligands. This conformational selection mechanism at quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.
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© 2015, Liu et al.
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Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition
eLife 4:e05767.
https://doi.org/10.7554/eLife.05767
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