title: A zinc complex of heparan sulfate destabilises lysozyme and alters its conformation.
abstract: The naturally occurring anionic cell surface polysaccharide heparan sulfate is involved in key biological activities and is implicated in amyloid formation. Following addition of Zn-heparan sulfate, hen lysozyme, a model amyloid forming protein, resembled β-rich amyloid by far UV circular dichroism (increased β-sheet: +25%), with a significantly reduced melting temperature (from 68 to 58 °C) by fluorescence shift assay. Secondary structure stability of the Zn-heparan sulfate complex with lysozyme was also distinct from that with heparan sulfate, under stronger denaturation conditions using synchrotron radiation circular dichroism. Changing the cation associated with heparan sulfate is sufficient to alter the conformation and stability of complexes formed between heparan sulfate and lysozyme, substantially reducing the stability of the protein. Complexes of heparan sulfate and cations, such as Zn, which are abundant in the brain, may provide alternative folding routes for proteins.
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Hughes
authors.forename: Rohanah
authors.initials: R
authors.lastname: Hussain
authors.forename: Cesare
authors.initials: C
authors.lastname: Cosentino
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
authors.forename: Giuliano
authors.initials: G
authors.lastname: Siligardi
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Yates
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rudd
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D004795:Enzyme Stability; D006497:Heparan Sulfate / Q000737:chemistry*; D009113:Muramidase / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D015032:Zinc / Q000737:chemistry*
chemical_list: D006497:Heparan Sulfate; D009113:Muramidase; D015032:Zinc; C421864:hen egg lysozyme