Rapid oligomer formation of human muscle acylphosphatase induced by heparan sulfate

Neda Motamedi-Shad, Tommaso Garfagnini, Amanda Penco, Annalisa Relini, Federico Fogolari, Alessandra Corazza, Gennaro Esposito, Francesco Bemporad, Fabrizio Chiti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalNature Structural and Molecular Biology
Issue number5
StatePublished - May 2012

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Rapid oligomer formation of human muscle acylphosphatase induced by heparan sulfate'. Together they form a unique fingerprint.

Cite this