Polyamines Mediate Folding of Primordial Hyperacidic Helical Proteins
| Autor: | Liam M. Longo, Dragana Despotovic, Dan S. Tawfik, Tali Scherf, Einav Aharon, Ita Gruić-Sovulj, Amit Kahana |
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| Rok vydání: | 2020 |
| Předmět: |
Protein Folding
Circular dichroism Glutamic Acid Context (language use) Biochemistry Article 03 medical and health sciences chemistry.chemical_compound Polyamines Nuclear Magnetic Resonance Biomolecular 030304 developmental biology 0303 health sciences Circular Dichroism Lysine 030302 biochemistry & molecular biology Proteins Hydrogen-Ion Concentration Folding (chemistry) Amino Acid Substitution chemistry Phosphodiester bond Nucleic acid Protein folding Chemical chaperone Polyamine Peptides and proteins Amines Monomers Organic polymers Titration |
| Zdroj: | Biochemistry |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/acs.biochem.0c00800 |
| Popis: | Polyamines are known to mediate diverse biological processes, and specifically to bind and stabilize compact conformations of nucleic acids, acting as chemical chaperones that promote folding by offsetting the repulsive negative charges of the phosphodiester backbone. However, whether and how polyamines modulate the structure and function of proteins remain unclear. In particular, early proteins are thought to have been highly acidic, like nucleic acids, due to a scarcity of basic amino acids in the prebiotic context. Perhaps polyamines, the abiotic synthesis of which is simple, could have served as chemical chaperones for such primordial proteins? We replaced all lysines of an ancestral 60-residue helix-bundle protein with glutamate, resulting in a disordered protein with 21 glutamates in total. Polyamines efficiently induce folding of this hyperacidic protein at submillimolar concentrations, and their potency scaled with the number of amine groups. Compared to cations, polyamines were several orders of magnitude more potent than Na+, while Mg2+ and Ca2+ had an effect similar to that of a diamine, inducing folding at approximately seawater concentrations. We propose that (i) polyamines and dications may have had a role in promoting folding of early proteins devoid of basic residues and (ii) coil–helix transitions could be the basis of polyamine regulation in contemporary proteins. |
| Databáze: | OpenAIRE |
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