Polymerization behavior of a bifunctional ubiquitin monomer as a function of the nucleophile site and folding conditions

Tal Moyal, Sudhir N. Bavikar, Subramanian Vedhanarayanan Karthikeyan, Hosahalli P. Hemantha, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Biopolymers with repeating modules composed of either folded peptides or tertiary protein domains are considered some of the basic biomaterials that nature has evolved to optimize for energy efficient synthesis and unique functions. Such biomaterials continue to inspire scientists to mimic their exceptional properties and the ways that nature adopts to prepare them. Ubiquitin chains represent another example of natures approach to use a protein-repeating module to prepare functionally important biopolymers. In the current work, we utilize a novel synthetic strategy to prepare bifunctional ubiquitin monomers having a C-terminal thioester and a nucleophilic 1,2-aminothiol at a desired position to examine their polymerization products under different conditions. Our study reveals that such analogues, when subjected to polymerization conditions under different folding states, afford distinct patterns of polymerization products where both the dynamic and the tertiary structures of the chains play important roles in such processes. Moreover, we also show that the presence of a specific ubiquitin-binding domain, which binds specifically to some of these chains, could interfere selectively with the polymerization outcome. Our study represents the first example of examining the polymerization of designed and synthetic repeating modules based on tertiary protein domains and affords early lessons in the design and synthesis of biomaterial. In regards to the ubiquitin system, our study may have implications on the ease of synthesis of ubiquitin chains with varying lengths and types for structural and functional analyses. Importantly, such an approach could also assist in understanding the enzymatic machinery and the factors controlling the assembly of these chains with a desired length.

Original languageEnglish
Pages (from-to)16085-16092
Number of pages8
JournalJournal of the American Chemical Society
Issue number38
StatePublished - 26 Sep 2012

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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