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Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
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On the evolution of protein-adenine binding
Aya Narunsky1, Amit Kessel1, Ron Solan1
1Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Ramat Aviv, Israel.
Summary
Proteins recognize ancient adenine ligands through conserved amino acid "themes," suggesting this fundamental molecular interaction evolved multiple times. This reveals insights into the origins of molecular recognition and protein evolution.
Area of Science:
- Biochemistry
- Structural Biology
- Evolutionary Biology
Background:
- Protein-ligand interactions are fundamental to biological processes.
- Adenine is a common and ancient ligand, crucial in biomolecules like DNA, RNA, and ATP.
- Understanding protein-adenine recognition can illuminate the evolution of molecular recognition.
Purpose of the Study:
- To investigate the mechanisms by which proteins recognize adenine.
- To identify conserved structural motifs and amino acid patterns involved in protein-adenine binding.
- To explore the evolutionary origins and recurrence of adenine binding in proteins.
Main Methods:
- Development of a computational pipeline to analyze protein-adenine complexes from the Protein Data Bank.
- Structural superposition of adenine fragments to identify conserved interaction patterns.
- Detection and analysis of hydrogen bonds mediating protein-adenine recognition.
- Identification of recurring amino acid segments ('themes') in protein binding sites.
Main Results:
- Characterization of protein-adenine interactions beyond the well-known Watson-Crick edge, indicating all adenine edges can mediate binding.
- Discovery of conserved amino acid 'themes' across diverse proteins that bind adenine-containing ligands.
- Identification of numerous proteins likely to bind adenine-containing ligands based on the presence of these themes.
- Evidence suggesting that adenine binding has arisen independently multiple times during evolution.
Conclusions:
- Protein-adenine recognition is mediated by conserved structural motifs and amino acid 'themes'.
- The evolution of molecular recognition likely involved multiple independent emergences of adenine binding.
- This study provides a framework for predicting novel protein-adenine interactions and understanding their evolutionary history.
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