Journal article
Elucidating glycosaminoglycan-protein-protein interactions using carbohydrate microarray and computational approaches
Proceedings of the National Academy of Sciences - PNAS, v 108(24), pp 9747-9752
14 Jun 2011
PMID: 21628576
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Glycosaminoglycan polysaccharides play critical roles in many cellular processes, ranging from viral invasion and angiogenesis to spinal cord injury. Their diverse biological activities are derived from an ability to regulate a remarkable number of proteins. However, few methods exist for the rapid identification of glycosaminoglycan-protein interactions and for studying the potential of glycosaminoglycans to assemble multimeric protein complexes. Here, we report a multidisciplinary approach that combines new carbohydrate microarray and computational modeling methodologies to elucidate glycosaminoglycan-protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 (FGF2) and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α (TNF-α). We also applied the approach to identify previously undescribed interactions between a specific sulfated epitope on chondroitin sulfate, CS-E, and the neurotrophins, a critical family of growth factors involved in the development, maintenance, and survival of the vertebrate nervous system. Our studies show for the first time that CS is capable of assembling multimeric signaling complexes and modulating neurotrophin signaling pathways. In addition, we identify a contiguous CS-E-binding site by computational modeling that suggests a potential mechanism to explain how CS may promote neurotrophin-tyrosine receptor kinase (Trk) complex formation and neurotrophin signaling. Together, our combined microarray and computational modeling methodologies provide a general, facile means to identify new glycosaminoglycan-protein-protein interactions, as well as a molecular-level understanding of those complexes.
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Details
- Title
- Elucidating glycosaminoglycan-protein-protein interactions using carbohydrate microarray and computational approaches
- Creators
- Claude J Rogers - Howard Hughes Medical InstitutePeter M ClarkSarah E TullyRavinder AbrolK Christopher GarciaWilliam A Goddard, 3rdLinda C Hsieh-Wilson
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 108(24), pp 9747-9752
- Publisher
- PNAS
- Grant note
- R01 NS073115 / NINDS NIH HHS R01 GM093627-02 / NIGMS NIH HHS 5T32 GM07737 / NIGMS NIH HHS Howard Hughes Medical Institute R01 GM093627 / NIGMS NIH HHS 5T32 GM07616 / NIGMS NIH HHS R01 GM093627-03 / NIGMS NIH HHS T32 GM007616 / NIGMS NIH HHS R01 NS071112 / NINDS NIH HHS R01 GM093627-01 / NIGMS NIH HHS T32 GM007737 / NIGMS NIH HHS 1R01 NS073115 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000291594000010
- Scopus ID
- 2-s2.0-79959954137
- Other Identifier
- 991019356341904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology