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Title: Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module

Abstract

The protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. This study suggests the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [2];  [1]
  1. Univ. of Colorado, Boulder, CO (United States)
  2. National Renewable Energy Lab. (NREL), Golden, CO (United States)
Publication Date:
Research Org.:
National Renewable Energy Lab. (NREL), Golden, CO (United States)
Sponsoring Org.:
USDOE Office of Energy Efficiency and Renewable Energy (EERE), Transportation Office. Bioenergy Technologies Office
OSTI Identifier:
1233680
Report Number(s):
NREL/JA-5100-65609
Journal ID: ISSN 2041-6520
Grant/Contract Number:  
AC36-08GO28308
Resource Type:
Accepted Manuscript
Journal Name:
Chemical Science
Additional Journal Information:
Journal Volume: 6; Journal Issue: 12; Related Information: Chemical Science; Journal ID: ISSN 2041-6520
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
09 BIOMASS FUELS; 59 BASIC BIOLOGICAL SCIENCES; protein glycosylation; biomolecular structure

Citation Formats

Guan, Xiaoyang, Chaffey, Patrick K., Zeng, Chen, Greene, Eric R., Chen, Liqun, Drake, Matthew R., Chen, Claire, Groobman, Ari, Resch, Michael G., Himmel, Michael E., Beckham, Gregg T., and Tan, Zhongping. Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module. United States: N. p., 2015. Web. doi:10.1039/C5SC02636A.
Guan, Xiaoyang, Chaffey, Patrick K., Zeng, Chen, Greene, Eric R., Chen, Liqun, Drake, Matthew R., Chen, Claire, Groobman, Ari, Resch, Michael G., Himmel, Michael E., Beckham, Gregg T., & Tan, Zhongping. Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module. United States. doi:10.1039/C5SC02636A.
Guan, Xiaoyang, Chaffey, Patrick K., Zeng, Chen, Greene, Eric R., Chen, Liqun, Drake, Matthew R., Chen, Claire, Groobman, Ari, Resch, Michael G., Himmel, Michael E., Beckham, Gregg T., and Tan, Zhongping. Mon . "Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module". United States. doi:10.1039/C5SC02636A. https://www.osti.gov/servlets/purl/1233680.
@article{osti_1233680,
title = {Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module},
author = {Guan, Xiaoyang and Chaffey, Patrick K. and Zeng, Chen and Greene, Eric R. and Chen, Liqun and Drake, Matthew R. and Chen, Claire and Groobman, Ari and Resch, Michael G. and Himmel, Michael E. and Beckham, Gregg T. and Tan, Zhongping},
abstractNote = {The protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. This study suggests the possibility of designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.},
doi = {10.1039/C5SC02636A},
journal = {Chemical Science},
number = 12,
volume = 6,
place = {United States},
year = {2015},
month = {9}
}

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Cited by: 11 works
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Works referenced in this record:

Specificity of O-glycosylation in enhancing the stability and cellulose binding affinity of Family 1 carbohydrate-binding modules
journal, May 2014

  • Chen, L.; Drake, M. R.; Resch, M. G.
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 21
  • DOI: 10.1073/pnas.1402518111

A clogged gutter mechanism for protease inhibitors
journal, July 2002

  • Radisky, E. S.; Koshland, D. E.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 16
  • DOI: 10.1073/pnas.112332899

The binding specificity and affinity determinants of family 1 and family 3 cellulose binding modules
journal, January 2003

  • Lehtio, J.; Sugiyama, J.; Gustavsson, M.
  • Proceedings of the National Academy of Sciences, Vol. 100, Issue 2
  • DOI: 10.1073/pnas.212651999

Site-selective chemical protein glycosylation protects from autolysis and proteolytic degradation
journal, August 2009


Glycoengineering: The effect of glycosylation on the properties of therapeutic proteins
journal, August 2005

  • Sinclair, Angus M.; Elliott, Steve
  • Journal of Pharmaceutical Sciences, Vol. 94, Issue 8
  • DOI: 10.1002/jps.20319

Protein Native-State Stabilization by Placing Aromatic Side Chains in N-Glycosylated Reverse Turns
journal, February 2011


Folding of glycoproteins: toward understanding the biophysics of the glycosylation code
journal, October 2009


Computational Investigation of Glycosylation Effects on a Family 1 Carbohydrate-binding Module
journal, December 2011

  • Taylor, Courtney B.; Talib, M. Faiz; McCabe, Clare
  • Journal of Biological Chemistry, Vol. 287, Issue 5
  • DOI: 10.1074/jbc.M111.270389

The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
journal, February 2009

  • Hanson, S. R.; Culyba, E. K.; Hsu, T. -L.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 9
  • DOI: 10.1073/pnas.0810318105

Isolated fungal cellulose terminal domains and a synthetic minimum analogue bind to cellulose
journal, January 1989


Recapitulation of IVIG Anti-Inflammatory Activity with a Recombinant IgG Fc
journal, April 2008


Analysis of the role of O-glycosylation in GH51 α- l -arabinofuranosidase from Pleurotus ostreatus : O-Glycosylation Role in α-
journal, May 2015

  • Amore, Antonella; Serpico, Annabel; Amoresano, Angela
  • Biotechnology and Applied Biochemistry, Vol. 62, Issue 6
  • DOI: 10.1002/bab.1325

Probing the Effect of the Outer Saccharide Residues of N -Linked Glycans on Peptide Conformation
journal, June 2001

  • O'Connor, Sarah E.; Pohlmann, Jens; Imperiali, Barbara
  • Journal of the American Chemical Society, Vol. 123, Issue 25
  • DOI: 10.1021/ja010094s

Glycoforms modify the dynamic stability and functional activity of an enzyme
journal, January 1994

  • Rudd, Pauline M.; Joao, Heidi C.; Coghill, Eva
  • Biochemistry, Vol. 33, Issue 1
  • DOI: 10.1021/bi00167a003

Glycoprotein Synthesis: An Update
journal, January 2009

  • Gamblin, David P.; Scanlan, Eoin M.; Davis, Benjamin G.
  • Chemical Reviews, Vol. 109, Issue 1
  • DOI: 10.1021/cr078291i

Glycosylation of Threonine of the Repeating Unit of RNA Polymerase II with β-Linked N -Acetylglucosame Leads to a Turnlike Structure
journal, November 1998

  • Simanek, Eric E.; Huang, Dee-Hua; Pasternack, Laura
  • Journal of the American Chemical Society, Vol. 120, Issue 45
  • DOI: 10.1021/ja982312w

Novel roles for the IgG Fc glycan: Fc glycan determines IgG antibody function
journal, January 2012

  • Anthony, Robert M.; Wermeling, Fredrik; Ravetch, Jeffrey V.
  • Annals of the New York Academy of Sciences, Vol. 1253, Issue 1
  • DOI: 10.1111/j.1749-6632.2011.06305.x

Structural Study on O -Glycopeptides:  Glycosylation-Induced Conformational Changes of O -GlcNAc, O -LacNAc, O -Sialyl-LacNAc, and O -Sialyl-Lewis-X Peptides of the Mucin Domain of MAdCAM-1
journal, March 1999

  • Wu, Wen-guey; Pasternack, Laura; Huang, Dee-Hua
  • Journal of the American Chemical Society, Vol. 121, Issue 11
  • DOI: 10.1021/ja983474v

Carbohydrate–Aromatic Interactions
journal, June 2012

  • Asensio, Juan Luis; Ardá, Ana; Cañada, Francisco Javier
  • Accounts of Chemical Research, Vol. 46, Issue 4
  • DOI: 10.1021/ar300024d

Protein-carbohydrate interactions: basic molecular features
journal, January 1989


Free sulfhydryl measurement as an indicator of antibody stability
journal, November 2008

  • Lacy, Eilyn R.; Baker, Margaret; Brigham-Burke, Michael
  • Analytical Biochemistry, Vol. 382, Issue 1
  • DOI: 10.1016/j.ab.2008.07.016

Erythropoietin Derived by Chemical Synthesis
journal, December 2013


Protein stability, flexibility and function
journal, August 2011

  • Teilum, Kaare; Olsen, Johan G.; Kragelund, Birthe B.
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1814, Issue 8
  • DOI: 10.1016/j.bbapap.2010.11.005

Recognition of Bisecting N -Acetylglucosamine: STRUCTURAL BASIS FOR ASYMMETRIC INTERACTION WITH THE MOUSE LECTIN DENDRITIC CELL INHIBITORY RECEPTOR 2
journal, October 2013

  • Nagae, Masamichi; Yamanaka, Kousuke; Hanashima, Shinya
  • Journal of Biological Chemistry, Vol. 288, Issue 47
  • DOI: 10.1074/jbc.M113.513572

Glycosylated linkers in multimodular lignocellulose-degrading enzymes dynamically bind to cellulose
journal, August 2013

  • Payne, Christina M.; Resch, Michael G.; Chen, Liqun
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 36
  • DOI: 10.1073/pnas.1309106110

N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability
journal, January 2012

  • Price, Joshua L.; Culyba, Elizabeth K.; Chen, Wentao
  • Biopolymers, Vol. 98, Issue 3
  • DOI: 10.1002/bip.22030

Synthesis at the Interface of Chemistry and Biology
journal, September 2009

  • Wu, Xu; Schultz, Peter G.
  • Journal of the American Chemical Society, Vol. 131, Issue 35
  • DOI: 10.1021/ja9026067

    Works referencing / citing this record:

    Role of glycosylation in nucleating protein folding and stability
    journal, July 2017

    • Jayaprakash, Nisha Grandhi; Surolia, Avadhesha
    • Biochemical Journal, Vol. 474, Issue 14
    • DOI: 10.1042/bcj20170111

    Just a spoonful of sugar: Short glycans affect protein properties and functions
    journal, March 2019

    • Bello, Claudia; Rovero, Paolo; Papini, Anna Maria
    • Journal of Peptide Science, Vol. 25, Issue 5
    • DOI: 10.1002/psc.3167

    Engineering enhanced cellobiohydrolase activity
    journal, March 2018


    The influence of different linker modifications on the catalytic activity and cellulose affinity of cellobiohydrolase Cel7A from Hypocrea jecorina
    journal, July 2017

    • Badino, Silke Flindt; Bathke, Jenny Kim; Sørensen, Trine Holst
    • Protein Engineering, Design and Selection, Vol. 30, Issue 7
    • DOI: 10.1093/protein/gzx036

    Distinct roles of N- and O-glycans in cellulase activity and stability
    journal, December 2017

    • Amore, Antonella; Knott, Brandon C.; Supekar, Nitin T.
    • Proceedings of the National Academy of Sciences, Vol. 114, Issue 52
    • DOI: 10.1073/pnas.1714249114