Aggregation of LEA proteins from Ramonda serbica: in silico vs. in vitro

Ana Pantelić1, Tatiana Ilina1, Dejana Milić1, Milan Senćanski2 and Marija Vidović1

1 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia

2 Institute of Nuclear Sciences VINCA, National Institute of Serbia, University of Belgrade, Serbia

anapantelic [at] imgge.bg.ac.rs

Abstract

Proteins known as Late Embryogenesis Abundant Proteins (LEAPs) are intrinsically disordered and play a crucial role in desiccation tolerance. Resurrection plants can withstand prolonged desiccation and fully recover their metabolic function the next day after watering. We identified, structurally characterized in silico, and categorized LEAPs in hydrated and desiccated leaves of the ancient resurrection plant Ramonda serbica to get more insights into their physiological functions.

A representative LEA4 protein highly accumulated under water scarcity was recombinantly produced and purified. It was predicted to be a highly disordered and polar protein. Structural models of dimers obtained by AlfaFold2 served as input for molecular simulation dynamics (MDS). Further, coarse-grain MDS using the GROMACS simulation package showed a high propensity of LEA4 protein to form dimers mostly by hydrophobic interactions. After the production phase, the obtained trajectory was analyzed for chain-chain contact for both cases λ=1.06 and 1.10. The dissociation constants Kd were calculated and were Kd ≈ 0.000075 M (75 μM) for the case λ=1.06 and Kd ≈ 0.0000758 M (75.8 μM) for the case λ=1.10., for the protein concentration Cp=8.91*10-5 M.

The results obtained by size exclusion chromatography, dynamic light scattering, and atomic forced microscopy confirmed that the selected LEA4 protein is aggregation-prone. Our results are important for further elucidating protective LEAP’s mechanism during desiccation. Structural flexibility and aggregation propensity of LEAP might be crucial in direct, or indirect (e.g. via LLPS) buffering free cellular water and maintaining the native conformations of biomolecules. We suggest that native or bioengineered LEAPs can be used to improve the drought resistance of crops.

Keywords: desiccation, intrinsically disordered proteins, late embryogenesis abundant proteins, molecular dynamic simulation.

Acknowledgement: This work was funded by the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (Contract No. 451-03-66/2024-03/200042) and by the Science Fund of the Republic of Serbia-RS (PROMIS project LEAPSyn-SCI, # 6039663).