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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 schematic illustration of the overall procedure used to prepare the glycoprotein structure pair sets (GP/P and P/P) from the PDB.
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f6: The schematic illustration of the overall procedure used to prepare the glycoprotein structure pair sets (GP/P and P/P) from the PDB.

Mentions: Figure 6 summarizes the overall procedure to prepare glycoprotein structure pairs for PDB structure analysis. We downloaded the PDB files of X-ray crystallographic structures that contain at least one protein and their resolution is ≤3 Å (72,578 files as of March 2013). For automatic sugar identification in the PDB files, we used Glycan Reader33. Glycan Reader detected 5,248 carbohydrate-containing PDB files (~7%) among all the downloaded files. A total of 9,728 protein chains that include covalently linked glycans or interact with glycan ligands were extracted. The protein chains with the covalently attached glycans were subsequently divided into N-linked and O-linked glycoproteins. A total of 4,802 protein chains were designated to N-linked glycoprotein chains (i.e., N-glycoproteins). The N-glycoproteins were then filtered to remove redundancy in each PDB file with a 90% sequence identity cutoff. The N-glycoproteins with less than 50 amino acids were also discarded because short proteins often do not have well-defined tertiary structures. A total of 2,384 N-glycoproteins were retained after the filtering process. Protein chains were also individually extracted from the downloaded PDB files that do not contain any carbohydrate molecules, followed by the same filtering process to remove redundant protein chains and small proteins. Finally, there were a total of 79,058 protein chains without associated carbohydrates.


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 schematic illustration of the overall procedure used to prepare the glycoprotein structure pair sets (GP/P and P/P) from the PDB.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: The schematic illustration of the overall procedure used to prepare the glycoprotein structure pair sets (GP/P and P/P) from the PDB.
Mentions: Figure 6 summarizes the overall procedure to prepare glycoprotein structure pairs for PDB structure analysis. We downloaded the PDB files of X-ray crystallographic structures that contain at least one protein and their resolution is ≤3 Å (72,578 files as of March 2013). For automatic sugar identification in the PDB files, we used Glycan Reader33. Glycan Reader detected 5,248 carbohydrate-containing PDB files (~7%) among all the downloaded files. A total of 9,728 protein chains that include covalently linked glycans or interact with glycan ligands were extracted. The protein chains with the covalently attached glycans were subsequently divided into N-linked and O-linked glycoproteins. A total of 4,802 protein chains were designated to N-linked glycoprotein chains (i.e., N-glycoproteins). The N-glycoproteins were then filtered to remove redundancy in each PDB file with a 90% sequence identity cutoff. The N-glycoproteins with less than 50 amino acids were also discarded because short proteins often do not have well-defined tertiary structures. A total of 2,384 N-glycoproteins were retained after the filtering process. Protein chains were also individually extracted from the downloaded PDB files that do not contain any carbohydrate molecules, followed by the same filtering process to remove redundant protein chains and small proteins. Finally, there were a total of 79,058 protein chains without associated carbohydrates.

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