Recent Publication from Metallo Group

Posted in News Story

Professor Steven Metallo of the ISMSM and his group recently published a paper, “Portability of a Small-Molecule Binding Site between Disordered Proteins” in Biomolecules. The research investigates the nature of small-molecule binding sites in intrinsically disordered proteins (IDPs) by transferring a short, small-molecule binding sequence derived from the c-Myc protein into another disordered protein. The group found that the sites were portable and retained binding function but that residues outside the binding site can have opposing effects on binding affinity depending on the broader protein context.

Graphical abstract of research, demonstrating small molecule binding capability.
The small molecule 34RH was shown to bind to the intrinsically disordered (IDP) the C-terminal domain of the oncoprotein cMyc. A short peptide from cMyc was shown to be sufficient to bind the small molecule and remained disordered when bound. This short binding sequence was added to another IDP, Max, to generate the protein MaxRH which was now able to bind to 34RH. These experiments demonstrated the portability of small molecule binding sequences between proteins.