Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1) forms amyloid-like fibrils by interaction with acidic phospholipids and inhibits Aβ aggregation.
Golgi-Associated plant Pathogenesis Related protein 1 (GAPR-1) is a mammalian protein that is a member of the Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis related proteins group 1 (CAP) superfamily of proteins. A role for the common CAP domain in the function of the diverse superfamily members has not been described so far. Here, we show by a combination of independent techniques including electron microscopy, Thioflavin T fluorescence, and circular dichroism that GAPR-1 has the capability to form amyloid-like fibrils in the presence of liposomes containing negatively charged lipids. Surprisingly, GAPR-1 was also shown to bind the amyloid-oligomer specific antibody A11 in the absence of lipids, indicating that GAPR-1 has an intrinsic tendency to form oligomers. This behavior is characteristic for proteins that interfere with Aβ aggregation and indeed we found that GAPR-1 effectively inhibited aggregation of Aβ(1-40) peptide. Immuno-dot blot analysis revealed that GAPR-1 binds to prefibrillar oligomeric Aβ structures during the early stages of fibril formation. Another CAP domain-containing protein, CRISP2, was also capable of forming fibrils, indicating that oligomerization and fibril formation is a shared characteristic between CAP family members. We suggest that the CAP domain may regulate protein oligomerization in a large variety of proteins that define the CAP superfamily.
Department of Biochemistry & Cell Biology and Institute of Biomembranes, Utrecht University , Utrecht , The Netherlands and.
Nick K
NK
Olrichs
Ajay K
AK
Mahalka
Dora
D
Kaloyanova
Paavo K
PK
Kinnunen
J
J
Bernd Helms
D000682:Amyloid / Q000737:chemistry*; D015815:Cell Adhesion Molecules; D002942:Circular Dichroism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry*
D000682:Amyloid; C062621:CRISP2 protein, human; D015815:Cell Adhesion Molecules; C458481:GLIPR2 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D010743:Phospholipids
Amyloid; CAP superfamily; CRISP2; GAPR-1; lipids