2N2K

Ensemble structure of the closed state of Lys63-linked diubiquitin in the absence of a ligand

Summary for 2N2K

• Entry DOI: 10.2210/pdb2n2k/pdb
• Related: 1UBQ 3H7P
• Descriptor: ubiquitin, S-[(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl] methanesulfonothioate (3 entities in total)
• Functional Keywords: polyubiquitin, ensemble structure, protein dynamics, ubiquitin signaling, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Ubiquitin: Cytoplasm : P0CG48 P0CG48
• Total number of polymer chains: 2
• Total formula weight: 17103.78

Authors

Liu, Z.,Gong, Z.,Tang, C. (deposition date: 2015-05-10, release date: 2015-07-08, Last modification date: 2024-11-13)

Primary citation

Liu, Z.,Gong, Z.,Jiang, W.X.,Yang, J.,Zhu, W.K.,Guo, D.C.,Zhang, W.P.,Liu, M.L.,Tang, C.
Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition.
Elife, 4:-, 2015

PubMed Abstract: A polyubiquitin comprises multiple covalently linked ubiquitins and recognizes myriad targets. Free or bound to ligands, polyubiquitins are 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 the quaternary level may be used by polyubiquitins of different lengths and linkages for target recognition.

PubMed: 26090905
DOI: 10.7554/eLife.05767

Experimental method

SOLUTION NMR