10.1021/ja3078736.s001
Tal Moyal
Tal
Moyal
Sudhir N. Bavikar
Sudhir N.
Bavikar
Subramanian Vedhanarayanan Karthikeyan
Subramanian Vedhanarayanan
Karthikeyan
Hosahalli P. Hemantha
Hosahalli P.
Hemantha
Ashraf Brik
Ashraf
Brik
Polymerization Behavior
of a Bifunctional Ubiquitin
Monomer as a Function of the Nucleophile Site and Folding Conditions
American Chemical Society
2012
polymerization products
module
biomaterial
protein domains
approach
synthesis
nature
Bifunctional Ubiquitin Monomer
length
bifunctional ubiquitin monomers
2012-09-26 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Polymerization_Behavior_of_a_Bifunctional_Ubiquitin_Monomer_as_a_Function_of_the_Nucleophile_Site_and_Folding_Conditions/2483443
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 nature’s
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.