Role of glycosylation in structure and stability of Erythrina corallodendron lectin (EcorL): A molecular dynamics study

Abstract

The effect of glycosylation on structure and stability of glycoproteins has been a topic of considerable interest. In this work, we have investigated the solution conformation of the oligosaccharide and its effect on the structure and stability of the glycoprotein by carrying out a series of long Molecular dynamics (MD) simulations on glycosylated Erythrina corallodendron lectin (EcorL) and nonglycosylated recombinant Erythrina corallodendron lectin (rEcorL). Our results indicate that, despite the similarity in overall three dimensional structures, glycosylated EcorL has lesser nonpolar solvent accessible surface area compared to nonglycosylated EcorL. This might explain the experimental observation of higher thermodynamic stability for glycosylated EcorL compared to nonglycosylated EcorL. Analysis of the simulation results indicates that, dynamic view of interactions between protein residues and oligosaccharide is entirely different from the static picture seen in the crystal structure. The oligosaccharide moiety had dynamically stable interactions with Lys 55 and Tyr 53, both of which are separated in sequence from the site of glycosylation, Asn 17. It is possible that glycosylation helps in forming long-range contacts between amino acids, which are separated in sequence and thus provides a folding nucleus. Thus our simulations not only reveal the conformations sampled by the oligosaccharide, but also provide novel insights into possible molecular mechanisms by which glycosylation can help in folding of the glycoprotein by formation of folding nucleus involving specific contacts with the oligosaccharide moiety.

Impact of glycosylation on stability, structure and unfolding of soybean agglutinin (SBA): an insight from thermal perturbation molecular dynamics simulations

“…It is seen that glycosylation has restricted the rotation of the Asn-75 side chain to a relatively smaller range. These results are consistent with the previous results of ECorL, where due to glycosylation at ASN-17, restriction of rotation was observed [42].…”

Using simulations to provide the framework for experimental protein folding studies

“…In addition, it participates in other earlier and significant nonnative contacts with various protein residues and water molecules, contributing actively to the folding process, not only to stabilize the final structure. The effect of a number of other common post-translational modifications of proteins, such as phosphorylation and glycosylation, are currently investigated in folding/unfolding simulations [72, 73]. In particular, glycosylation can help the folding process through the formation of specific long-range contacts involving the oligosaccharide moiety in the folding nucleus [73], contributing also to enhance the thermal stability of the protein native state [74].…”

Insights into the structural stability of Bax from molecular dynamics simulations at high temperatures

“…[40][41][42][43][44][45][46] A recent work published in this fine journal used MD simulations at temperatures up to 600 K to study the stability of an important protein, focusing on the role of glycosylation therein. 47 Bax has been the object of several biophysical, chemical, and computational studies. Nevertheless, the atomic-level description of Bax stability remains to be fully explored.…”