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Predicting glycosaminoglycan surface protein interactions and implications for studying axonal growth.

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Title: Predicting glycosaminoglycan surface protein interactions and implications for studying axonal growth.
Authors: Griffith, Adam R.1,2, Abrol, Ravinder1,2, Goddard III, William A.1,2, Rogers, Claude J.2, Miller, Gregory M.2, Hsieh-Wilson, Linda C.2
Source: Proceedings of the National Academy of Sciences of the United States of America. 12/26/2017, Vol. 114 Issue 52, p13697-13702. 6p.
Subjects: Glycosaminoglycans, Cell membranes, Axons, Carbohydrate analysis, Protein binding, Chondroitin sulfates, Heparin, Molecular docking
Abstract: Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various proteinbinding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which display varied stereochemistry, chain lengths, and patterns of sulfation. GAG--protein interactions participate in neuronal development, angiogenesis, spinal cord injury, viral invasion, and immune response. Unfortunately, little structural information is available for these complexes; indeed, for the highly sulfated chondroitin sulfate motifs, CS-E and CS-D, there are no structural data. We describe here the development and validation of the GAG-Dock computational method to predict accurately the binding poses of protein-bound GAGs. We validate that GAG-Dock reproduces accurately (<1-Å rmsd) the crystal structure poses for four known heparin--protein structures. Further, we predict the pose of heparin and chondroitin sulfate derivatives bound to the axon guidance proteins, protein tyrosine phosphatase σ (RPTPσ), and Nogo receptors 1-3 (NgR1-3). Such predictions should be useful in understanding and interpreting the role of GAGs in neural development and axonal regeneration after CNS injury. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
Abstract:Cell-surface carbohydrates play important roles in numerous biological processes through their interactions with various proteinbinding partners. These interactions are made possible by the vast structural diversity of carbohydrates and the diverse array of carbohydrate presentations on the cell surface. Among the most complex and important carbohydrates are glycosaminoglycans (GAGs), which display varied stereochemistry, chain lengths, and patterns of sulfation. GAG--protein interactions participate in neuronal development, angiogenesis, spinal cord injury, viral invasion, and immune response. Unfortunately, little structural information is available for these complexes; indeed, for the highly sulfated chondroitin sulfate motifs, CS-E and CS-D, there are no structural data. We describe here the development and validation of the GAG-Dock computational method to predict accurately the binding poses of protein-bound GAGs. We validate that GAG-Dock reproduces accurately (<1-Å rmsd) the crystal structure poses for four known heparin--protein structures. Further, we predict the pose of heparin and chondroitin sulfate derivatives bound to the axon guidance proteins, protein tyrosine phosphatase σ (RPTPσ), and Nogo receptors 1-3 (NgR1-3). Such predictions should be useful in understanding and interpreting the role of GAGs in neural development and axonal regeneration after CNS injury. [ABSTRACT FROM AUTHOR]
ISSN:00278424
DOI:10.1073/pnas.1715093115