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PMID:15522881

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Citation

Söderberg, L, Kakuyama, H, Möller, A, Ito, A, Winblad, B, Tjernberg, LO and Näslund, J (2005) Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide-binding site. J. Biol. Chem. 280:1007-15

Abstract

Amyloid beta-peptide (Abeta) deposition into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Other proteins co-deposit with Abeta in plaques, and one recently identified amyloid-associated protein is the collagen-like Alzheimer amyloid plaque component CLAC. It is not known how CLAC deposition affects Abeta plaque genesis and the progress of the disease. Here, we studied the in vitro properties of CLAC purified from a mammalian expression system. CLAC displays features characteristic of a collagen protein, e.g. it forms a partly protease-resistant triple-helical structure, exhibits an intermediate affinity for heparin, and is glycosylated. Purified CLAC was also used to investigate the interaction between CLAC and Abeta. Using a solid-phase binding assay, we show that CLAC bound with a similar affinity to aggregates formed by Abeta-(1-40) and Abeta-(1-42) and that the interaction was impaired by increasing salt concentrations. An 8-residue-long sequence located in non-collagenous domain 2 of CLAC was found to be crucial for the interaction with Abeta. These findings may be useful for future therapeutic interventions aimed at finding compounds that modulate the binding of CLAC to Abeta deposits.

Links

PubMed Online version:10.1074/jbc.M403628200

Keywords

Alzheimer Disease/metabolism; Amino Acid Motifs; Amino Acid Sequence; Amyloid beta-Peptides/metabolism; Binding Sites; Cell Line; Circular Dichroism; Glycosylation; Heparin/metabolism; Humans; Mutagenesis/genetics; N-Acetylneuraminic Acid/metabolism; Non-Fibrillar Collagens/chemistry; Non-Fibrillar Collagens/genetics; Non-Fibrillar Collagens/isolation & purification; Non-Fibrillar Collagens/metabolism; Pepsin A/metabolism; Protein Binding; Protein Structure, Quaternary/drug effects; Protein Structure, Tertiary/drug effects; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/isolation & purification; Recombinant Proteins/metabolism; Salts/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:COPA1

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BXS0-3

F

Seeded From UniProt

complete

HUMAN:COPA1

enables

GO:0001540: amyloid-beta binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:COPA1

enables

GO:0008201: heparin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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