Glycans modulate lipid binding in Lili-Mip lipocalin protein: insights from molecular simulations and protein network analyses

SureshKumar, H and Appadurai, R and Srivastava, A (2024) Glycans modulate lipid binding in Lili-Mip lipocalin protein: insights from molecular simulations and protein network analyses. In: Glycobiology, 34 (2).

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Abstract

The unique viviparous Pacific Beetle cockroaches provide nutrition to their embryo by secreting milk proteins Lili-Mip, a lipid-binding glycoprotein that crystallises in-vivo. The resolved in-vivo crystal structure of variably glycosylated Lili-Mip shows a classical Lipocalin fold with an eight-stranded antiparallel beta-barrel enclosing a fatty acid. The availability of physiologically unaltered glycoprotein structure makes Lili-Mip a very attractive model system to investigate the role of glycans on protein structure, dynamics, and function. Towards that end, we have employed all-atom molecular dynamics simulations on various glycosylated stages of a bound and free Lili-Mip protein and characterised the impact of glycans and the bound lipid on the dynamics of this glycoconjugate. Our work provides important molecular-level mechanistic insights into the role of glycans in the nutrient storage function of the Lili-Mip protein. Our analyses show that the glycans stabilise spatially proximal residues and regulate the low amplitude opening motions of the residues at the entrance of the binding pocket. Glycans also preserve the native orientation and conformational flexibility of the ligand. However, we find that either deglycosylation or glycosylation with high-mannose and paucimannose on the core glycans, which better mimic the natural insect glycosylation state, significantly affects the conformation and dynamics. A simple but effective distance- and correlation-based network analysis of the protein also reveals the key residues regulating the barrel's architecture and ligand binding characteristics in response to glycosylation. © The Author(s) 2023. Published by Oxford University Press. All rights reserved.

Item Type:	Journal Article
Publication:	Glycobiology
Publisher:	Oxford University Press
Additional Information:	The copyright for this article belongs to Oxford University Press.
Keywords:	glycan; glycoprotein; lipocalin; glycoprotein; ligand; lipid; lipocalin; polysaccharide; protein binding, Article; beetle; cockroach; controlled study; deglycosylation; eigenvector centrality; embryo; hydrogen bond; ligand binding; molecular dynamics; network analysis; nonhuman; protein binding; protein conformation; protein structure; root mean squared error; viviparity; waste, Glycoproteins; Ligands; Lipids; Lipocalins; Polysaccharides; Protein Binding
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	22 May 2024 04:01
Last Modified:	22 May 2024 04:01
URI:	https://eprints.iisc.ac.in/id/eprint/84829

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