Linkage-specific conformational ensembles of non-canonical polyubiquitin chains.

@article{Castaeda2016LinkagespecificCE,
  title={Linkage-specific conformational ensembles of non-canonical polyubiquitin chains.},
  author={Carlos A. Casta{\~n}eda and Apurva Chaturvedi and Christina M. Camara and Joseph E. Curtis and Susan Krueger and David Fushman},
  journal={Physical chemistry chemical physics : PCCP},
  year={2016},
  volume={18 8},
  pages={
          5771-88
        }
}
Polyubiquitination is a critical protein post-translational modification involved in a variety of processes in eukaryotic cells. The molecular basis for selective recognition of the polyubiquitin signals by cellular receptors is determined by the conformations polyubiquitin chains adopt; this has been demonstrated for K48- and K63-linked chains. Recent studies of the so-called non-canonical chains (linked via K6, K11, K27, K29, or K33) suggest they play important regulatory roles in growth… 

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References

SHOWING 1-10 OF 62 REFERENCES

Solution Conformation of Lys63-linked Di-ubiquitin Chain Provides Clues to Functional Diversity of Polyubiquitin Signaling*

NMR methods are used to determine the structure of a Lys63-linked di-ubiquitin chain and show that both ubiquitin domains in this chain can bind a ubiquit in-associated domain from HHR23A independently and in a mode similar to that for mono-ubsitin.

Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations

This work provides a method to assemble Lys33-linked polyUb that will allow further characterization of this atypical chain type and identifies an enzymatic system for the large-scale assembly of Lys33 chains by combining the HECT (homologous to the E6–AP C-terminus) E3 ligase AREL1 with linkage selective deubiquitinases (DUBs).

Nonenzymatic assembly of natural polyubiquitin chains of any linkage composition and isotopic labeling scheme.

This paper presents a robust, efficient, and widely accessible method for controlled iterative nonenzymatic assembly of polyubiquitin chains using recombinant ubiquitin monomers as the primary building blocks and demonstrates the ability to obtain, by high-resolution NMR, residue-specific information on ubiquitIn units at any desired position in such chains.

Segmental isotopic labeling of ubiquitin chains to unravel monomer-specific molecular behavior.

Uncovering the mechanisms that allow various polyUb chains to serve as distinct molecular signals requires the ability to make these chains with the native connectivity, defined linkage and composition, controlled length, and in sufficient quantities for structural/biochemical studies.
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