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Rapid Protein Oligomer Formation of Human Muscle Acylphosphatase Induced by Heparan Sulfate
- Publication Year :
- 2012
-
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.
- Subjects :
- Amyloid
Plasma protein binding
Acylphosphatase
Protein Structure, Secondary
Extracellular matrix
chemistry.chemical_compound
Protein structure
Structural Biology
Protein aggregation
Fibrillogenesis and heparan sulphate
GAG-induced aggregation
Native state
Extracellular
Humans
Molecular Biology
Chemistry
Muscles
Heparan sulfate
Acid Anhydride Hydrolases
Biochemistry
Mutation
Heparitin Sulfate
Protein Multimerization
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c0c6b6d7eacc8b2a406010d7629f7881