Extracellular mammalian polysaccharides: glycosaminoglycans and proteoglycans

Beaty, Narlin; Mello, Robert J.

doi:10.1016/0378-4347(87)80009-9

Cited by 62 publications

(29 citation statements)

References 183 publications

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“…Schematic representation of typical disaccharide repeating units for heparin, ChA, DS, and heparan sulfate. Color coding represents different sugar types, highlighting differences in sulfation (8,51). The triple sulfated disaccharide unit of heparin (top) makes up 80 -90% of the polymer.…”

Section: Sct and Heparin Form A Binding Complex With ␣-Helicalmentioning

confidence: 99%

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How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin

Malmos

Bjerring

Jessen

et al. 2016

Journal of Biological Chemistry

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Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT⅐heparin complexes form ␤-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys 11 but makes changes to Val 8 on the exterior side of the ␤-strand, possibly through contacts to Lys 18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT.

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Section: Sct and Heparin Form A Binding Complex With ␣-Helicalmentioning

confidence: 99%

“…1). Heparin is the GAG with the most consistent repetitive disaccharide composition, whereas other GAGs follow a less strictly repetitive sulfation pattern (8).…”

mentioning

confidence: 99%

How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin

Malmos

Bjerring

Jessen

et al. 2016

Journal of Biological Chemistry

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“…In particular, the typical cationic dyes and stains detect almost any highly negatively charged component, surface, or tissue. Later, electrophoresis in agarose gels or cellulose acetate membranes was used to analyze intact GAG components (reviewed in Beaty and Mello, 1987;Kodama et al, 1988), but preparations of these polydisperse molecules were often cross-contaminated. Fortunately, various glycosidases with rather narrow GAG substrate specificity have become commercially available (reviewed in Linhardt et al, 1986).…”

Section: Gag Analyses Past and Presentmentioning

confidence: 99%

Evolution of glycosaminoglycans and their glycosyltransferases: Implications for the extracellular matrices of animals and the capsules of pathogenic bacteria

DeAngelis

2002

Anat. Rec.

100

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Glycosaminoglycans (linear polysaccharides with a repeating disaccharide backbone containing an amino sugar) are essential components of extracellular matrices of animals. These complex molecules play important structural, adhesion, and signaling roles in mammals. Direct detection of glycosaminoglycans has been reported in a variety of organisms, but perhaps more definitive tests for the glycosyltransferase genes should be utilized to clarify the distribution of glycosaminoglycans in metazoans. Recently, glycosyltransferases that form the hyaluronan, heparin/heparan, or chondroitin backbone were identified at the molecular level. The three types of glycosyltransferases appear to have evolved independently based on sequence comparisons and other characteristics. All metazoans appear to possess heparin/heparan. Chondroitin is found in some worms, arthropods, and higher animals. Hyaluronan is found only in two of the three main branches of chordates. The presence of several types of glycosaminoglycans in the body allows multiple communication channels and adhesion systems to operate simultaneously. Certain pathogenic bacteria produce extracellular coatings, called capsules, which are composed of glycosaminoglycans that increase their virulence during infection. The capsule helps shield the microbe from the host defenses and/or modulates host physiology. The bacterial and animal polysaccharides are chemically identical or at least very similar. Therefore, no immune response is generated, in contrast to the vast majority of capsular polymers from other bacteria. In microbial systems, it appears that in most cases functional convergent evolution of glycosaminoglycan glycosyltransferases occurred, rather than direct horizontal gene transfer from their vertebrate hosts. Anat Rec 268: 317-326, 2002.

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“…Numerous analytical methods such as cellulose acetate membrane electrophoresis, paper chromatography, gas chromatography, affinity chromatography, HPLC, capillary electrophoretic analysis have been developed and applied to quantitative, qualitative, and structural analysis of GAGs. 19,20 However, plasma GAG structures have not yet been fully characterized due to a general lack of robust and sensitive analytical tools. There are no standardized methods for serum/plasma GAG isolation and quantification.…”

Section: Introductionmentioning

confidence: 99%