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Supramolecular protein assemblies: A rational design approach  Jul 23, 2019

Self assembly of proteins into superstructures is of interest considering its implications in variety of applications such as gene delivery, vaccine design and diagnostics. Genetic engineering involving computational methods and rational design strategies have been employed to design protein superstructures with high accuracy. However, most of the reported protein superstructure lack dynamic behavior which is essential to exhibit higher-order functions. Chemical methods do provide an opportunity to design dynamic protein assemblies, but the assemblies thus generated are mostly polydisperse and difficult to make.

Dr. Britto Sandanaraj at IISER Pune has developed a chemical method for the design of dynamic supramolecular protein complexes. The strategy involves using an in-house developed micelle-assisted protein labeling technology to synthesize libraries of facially amphiphilic semi-synthetic proteins. The synthesized proteins resemble small molecule surfactant molecule having a hydrophilic head and hydrophobic tail in terms of their of their amphiphilic character, except that their size is relatively big. These facially amphiphilic proteins self-assemble to form protein superstructures through hydrophobic interactions.

According to Dr. Sandanaraj, the novelty of this approach lies in the fact that the size, shape, molecular weight and surface charge of the protein complex can be systematically tuned at nanometer level by changing protein, linker length and tail length and volume. The details can be found in this recent paper published by the group (citation shown below).

The degree of complex formation is dictated by the strong attractive interaction between hydrophobic tail and electrostatic repulsion between protein head groups.

Furthermore, the team at IISER Pune has designed for the first time photoresponsive protein nanoassemblies using this approach, which can be used as a stimuli responsive nanosystem (as pictured here).

This work received funding from DST‐SERB, DBT, and IISER Pune.

Article Citation: Rational Design of Supramolecular Dynamic Protein Assemblies by Using a Micelle-Assisted Activity-Based Protein-Labeling Technology. Britto S. Sandanaraj, Mullapudi Mohan Reddy, Pavankumar Janardhan Bhandari, Sugam Kumar, Vinod K. Aswal. Chem. Eur. J. 2018, 24, 16085–16096. https://doi.org/10.1002/chem.201802824


Compiled with inputs from Dr. Britto Sandanaraj, IISER Pune
Reported by Dr. Madhura Joglekar