New progress in the mechanism of Lys63-linked ubiquitin chain recognizing specific targets

  • Posted on: 6 July 2015
  • By: zhouxue

Tang and colleagues revealed a hidden mechanism of how Lys63-linked ubiquitin recognize their target proteins, which was published recently in elife.

http://elifesciences.org/content/early/2015/06/19/eLife.05767

Ubiquitin is a 76-residue signaling protein found ubiquitously in cell, ubquitins are linked together via N terminus or one of the seven lysines and lead to the formation of polymeric chains chains of different linkage adopt distinct conformations to specifically recognize respective targets and they are involved in many biologically relevant process such as NF-κB signal pathway, DNA damage repair, proteasomal degradation. Structure studies have indicated that K63-Ub2 predominantly exists in open structure either free or in complex with many target proteins, K63-Ub2 has also been found adopt closed conformation with certain target.

It was not clear whether the protein could adopt closed conformation without first binding to a target protein until tang used a technique known as NMR to investigate the conformation dynamics of K63-Ub2 in solution. Tang and colleagues have combined paramagnetic relaxation enhancement with structural computation to demonstrate that K63-Ub2 populates considerable closed conformation, further analysis indicated that closed conformation can be divided into at least two groups to accommodate different target proteins. The research uncovered the high- resolution closed conformation K63-Ub2 adopted in solution and revealed that the mechanism of binding is conformational selection. Further work will demonstrate whether other polyubiquitin chains recognize their partners in a similar manner.

The work has been supported by the National Natural Science Foundation of China (31225007 and 31170728) and by the Chinese Ministry of Science and Technology (2013CB910200) . Dr. Chun Tang is an International Early Career Scientist grant of the Howard Hughes Medical Institute. 

 

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