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Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study.

Lee HS, Qi Y, Im W - Sci Rep (2015)

Bottom Line: There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties.Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability.Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, United States.

ABSTRACT
N-linked glycosylation is one of the most important, chemically complex, and ubiquitous post-translational modifications in all eukaryotes. The N-glycans that are covalently linked to proteins are involved in numerous biological processes. There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties. In this study, the impacts of N-glycans on protein structure and dynamics are systematically investigated using an integrated computational approach of the Protein Data Bank structure analysis and atomistic molecular dynamics simulations of glycosylated and deglycosylated proteins. Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability. Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.

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The cartoon representation of six glycoproteins (PDB id + chain id) used for MD simulation study.The stick representation is used to display N-linked glycans.
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f2: The cartoon representation of six glycoproteins (PDB id + chain id) used for MD simulation study.The stick representation is used to display N-linked glycans.

Mentions: A systematic analysis of PDB protein structures can provide valuable insight into the extent of structural changes induced by N-glycosylation. However, the PDB glycoprotein structures are “static” and thus they cannot be directly used to extract the extent of changes in protein dynamics upon glycosylation. To better understand the effect of N-glycosylation on protein structure and dynamics, six representative glycoproteins were elaborately selected from the PDB, and three independent 200-ns MD simulations were performed for both glycosylated and deglycosylated forms of each protein (Tables S1 and S2; see Methods for detailed descriptions). The global topologies of the six representative glycoproteins are shown in Figure 2.


Effects of N-glycosylation on protein conformation and dynamics: Protein Data Bank analysis and molecular dynamics simulation study.

Lee HS, Qi Y, Im W - Sci Rep (2015)

The cartoon representation of six glycoproteins (PDB id + chain id) used for MD simulation study.The stick representation is used to display N-linked glycans.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352867&req=5

f2: The cartoon representation of six glycoproteins (PDB id + chain id) used for MD simulation study.The stick representation is used to display N-linked glycans.
Mentions: A systematic analysis of PDB protein structures can provide valuable insight into the extent of structural changes induced by N-glycosylation. However, the PDB glycoprotein structures are “static” and thus they cannot be directly used to extract the extent of changes in protein dynamics upon glycosylation. To better understand the effect of N-glycosylation on protein structure and dynamics, six representative glycoproteins were elaborately selected from the PDB, and three independent 200-ns MD simulations were performed for both glycosylated and deglycosylated forms of each protein (Tables S1 and S2; see Methods for detailed descriptions). The global topologies of the six representative glycoproteins are shown in Figure 2.

Bottom Line: There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties.Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability.Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biosciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, United States.

ABSTRACT
N-linked glycosylation is one of the most important, chemically complex, and ubiquitous post-translational modifications in all eukaryotes. The N-glycans that are covalently linked to proteins are involved in numerous biological processes. There is considerable interest in developments of general approaches to predict the structural consequences of site-specific glycosylation and to understand how these effects can be exploited in protein design with advantageous properties. In this study, the impacts of N-glycans on protein structure and dynamics are systematically investigated using an integrated computational approach of the Protein Data Bank structure analysis and atomistic molecular dynamics simulations of glycosylated and deglycosylated proteins. Our study reveals that N-glycosylation does not induce significant changes in protein structure, but decreases protein dynamics, likely leading to an increase in protein stability. Overall, these results suggest not only a common role of glycosylation in proteins, but also a need for certain proteins to be properly glycosylated to gain their intrinsic dynamic properties.

Show MeSH