Effect of glycosylation on the structure of <i>Erythrina corallodendron</i> lectin

Kulkarni, Kiran; Srivastava, Anand; Mitra, N. K.; Sharon, Nathan; Surolia, Avadhesha; Vijayan, M.; Suguna, K.

doi:10.1002/prot.20168

Cited by 22 publications

(12 citation statements)

References 41 publications

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“…Initially this new mode of quaternary association was attributed to the presence of the oligosaccharide 23. However, subsequent elucidation of the crystal structure of the recombinant form of EcorL (rEcorL)28, 29 lacking glycosylation revealed that, it had identical quaternary association as the native glycosylated form. This indicated that glycosylation per se could not have been the cause for a new mode of quaternary association.…”

Section: Introductionmentioning

confidence: 99%

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

2011

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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.

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Section: Introductionmentioning

confidence: 99%

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

2011

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“…We originally ascribed this difference to the interference by the N-linked carbohydrate of ECorL in forming the canonical structure. This interpretation has been proven to be incorrect, since in a recent joint study with Avadesha Surolia and colleagues from the Indian Institute of Scientific Research, Bangalore, the quaternary structure of the bacterially expressed ECorL, devoid of carbohydrate, was the same as that of the native one [28]. Examination of the three-dimensional structure of the ECorL-lactose complex, as well as site-directed mutagenesis of the lectin carried out by Rivka Adar together with Hansjörg Streicher, postdoctoral fellow from the University of Konstanz, has led to the identification of the residues of the lectin that are essential for ligand binding; they were found to be identical to those of other legume lectins with different carbohydrate specificities as well [29,30].…”

Section: Bacterial Lectins Cell Recognition and Anti Adhesion Therapmentioning

confidence: 86%

A life with lectins

Sharon

2005

CMLS, Cell. Mol. Life Sci.

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“…Potentially, proper folding of the protein could have been due to induction by intramolecular interaction of the amino acid side chains with the added glycans, as hypothesized in the folding of Erythrina corallodendron lectin (31,44). However, although CD36N8 -10 and CD36N1-7 do not share a common glycosylation site, they are both able to traffic to the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

The Human Scavenger Receptor CD36

Hoosdally

Andress

Wooding

et al. 2009

Journal of Biological Chemistry

110

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Human CD36 is a class B scavenger receptor expressed in a variety of cell types such as macrophage and adipocytes. This plasma membrane glycoprotein has a wide range of ligands including oxidized low density lipoprotein and long chain fatty acids which involves the receptor in diseases such as atherosclerosis and insulin resistance. CD36 is heavily modified posttranslationally by N-linked glycosylation, and 10 putative glycosylation sites situated in the large extracellular loop of the protein have been identified; however, their utilization and role in the folding and function of the protein have not been characterized. Using mass spectrometry on purified and peptide N-glycosidase F-deglycosylated CD36 and also by comparing the electrophoretic mobility of different glycosylation site mutants, we have determined that 9 of the 10 sites can be modified by glycosylation. Flow cytometric analysis of the different glycosylation mutants expressed in mammalian cells established that glycosylation is necessary for trafficking to the plasma membrane. Minimally glycosylated mutants that supported trafficking were identified and indicated the importance of carboxyl-terminal sites Asn-247, Asn-321, and Asn-417. However, unlike SRBI, no individual site was found to be essential for proper trafficking of CD36. Surprisingly, these minimally glycosylated mutants appear to be predominantly core-glycosylated, indicating that mature glycosylation is not necessary for surface expression in mammalian cells. The data also show that neither the nature nor the pattern of glycosylation is relevant to binding of modified low density lipoprotein.Human CD36, originally identified in platelets as glycoprotein IV (1), is a class B scavenger receptor localized to the plasma membrane. It is not expressed ubiquitously but is present in a variety of different cells and tissue types including epithelial cells (2), macrophages (3), endothelial cells of the microvasculature (4), and smooth muscle (5). Its function is complex, and its involvement in different disease scenarios, such as cancer (6), atherosclerosis (3,7,8), malaria (9), and insulin resistance (10), most likely reflects the interaction of the receptor with a particular ligand in a specific cell type. For example, CD36 expressed in monocytic macrophages functions as a scavenger receptor for the uptake of oxidized LDL 2 (3, 11). Under certain physiological conditions, this results in the lipid loading of macrophages at the site of tissue damage in the arterial wall, leading to foam cell formation and plaque development, a key early stage in the pathogenesis of atherosclerosis (8,12). In fat and muscle cells, CD36 plays an essential role in lipid homeostasis by uptake of long chain fatty acids (13). In this case CD36 deficiency has been linked to disorders in lipid metabolism, giving rise to increased incidences of insulin resistance and cardiomyopathies (11,14,15).Although much is known about the function of CD36, less is known about its structure. CD36 has no bacterial homologues but is...

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Effect of glycosylation on the structure of Erythrina corallodendron lectin

Cited by 22 publications

References 41 publications

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

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

A life with lectins

The Human Scavenger Receptor CD36

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