title: Rapid oligomer formation of human muscle acylphosphatase induced by heparan sulfate.
abstract: Many human diseases are caused by the conversion of proteins from their native state into amyloid fibrils that deposit in the extracellular space. Heparan sulfate, a component of the extracellular matrix, is universally associated with amyloid deposits and promotes fibril formation. The formation of cytotoxic prefibrillar oligomers is challenging to study because of its rapidity, transient appearance and the heterogeneity of species generated. The process is even more complex with agents such as heparan sulfate. Here we have used a stopped-flow device coupled to turbidometry detection to monitor the rapid conversion of human muscle acylphosphatase into oligomers with varying heparan sulfate and protein concentrations. We also analyzed mutants of the 15 basic amino acids of acylphosphatase, identifying the residues primarily involved in heparan sulfate-induced oligomerization of this protein and tracing the process with unprecedented molecular detail.
authors.affiliation: Dipartimento di Biochimica, Università di Firenze, Florence, Italy.
authors.forename: Neda
authors.initials: N
authors.lastname: Motamedi-Shad
authors.forename: Tommaso
authors.initials: T
authors.lastname: Garfagnini
authors.forename: Amanda
authors.initials: A
authors.lastname: Penco
authors.forename: Annalisa
authors.initials: A
authors.lastname: Relini
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
authors.forename: Francesco
authors.initials: F
authors.lastname: Bemporad
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D009132:Muscles / Q000201:enzymology* / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000682:Amyloid; D006497:Heparan Sulfate; D000097024:Acylphosphatase