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Aromatic-aromatic interactions drive fold switch of GA95 and GB95 with three residue difference
Chen Chen1,2, Zeting Zhang1,2, Mojie Duan3
1Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan National Laboratory for Optoelectronics, Wuhan Institute of Physics and Mathematics, Innovation Academy of Precision Measurement, Chinese Academy of Sciences Wuhan 430071 China conggangli@apm.ac.cn zhangzeting@wipm.ac.cn.
Abstract:
Proteins typically adopt a single fold to carry out their function, but metamorphic proteins, with multiple folding states, defy this norm. Deciphering the mechanism of conformational interconversion of metamorphic proteins is challenging. Herein, we employed nuclear magnetic resonance (NMR), circular dichroism (CD), and all-atom molecular dynamics (MD) simulations to elucidate the mechanism of fold switching in proteins GA95 and GB95, which share 95% sequence homology. The results reveal that long-range interactions, especially aromatic π-π interactions involving residues F52, Y45, F30, and Y29, are critical for the protein switching from a 3α to a 4β + α fold. This study contributes to understanding how proteins with highly similar sequences fold into distinct conformations and may provide valuable insights into the protein folding code.
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