TY - JOUR
T1 - Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild-type rats
AU - Christensen, Line Friis Bakmann
AU - Alijanvand, Saeid Hadi
AU - Burdukiewicz, Michał
AU - Herbst, Florian Alexander
AU - Kjeldal, Henrik
AU - Dueholm, Morten Simonsen
AU - Otzen, Daniel E.
N1 - Publisher Copyright:
© 2021 The Protein Society.
PY - 2021/9
Y1 - 2021/9
N2 - Cross seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson's disease (PD). This is particularly pertinent in view of the growing number of functional (i.e., benign and useful) amyloid proteins discovered in bacteria. Here we identify two amyloidogenic proteins, Pr12 and Pr17, in fecal matter from PD transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid (FA). Both proteins show robust aggregation into ThT-positive aggregates that contain higher-order β-sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formed in vitro showed significant resistance against FA, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregation in vitro. Thus, amyloidogenicity does not per se lead to an ability to cross-seed fibrillation of αSN. Our results support the use of proteomics and FA to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes.
AB - Cross seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson's disease (PD). This is particularly pertinent in view of the growing number of functional (i.e., benign and useful) amyloid proteins discovered in bacteria. Here we identify two amyloidogenic proteins, Pr12 and Pr17, in fecal matter from PD transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid (FA). Both proteins show robust aggregation into ThT-positive aggregates that contain higher-order β-sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formed in vitro showed significant resistance against FA, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregation in vitro. Thus, amyloidogenicity does not per se lead to an ability to cross-seed fibrillation of αSN. Our results support the use of proteomics and FA to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes.
KW - fibrillation
KW - functional amyloid
KW - microbiome
KW - Parkinson's disease
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85107377559&partnerID=8YFLogxK
U2 - 10.1002/pro.4137
DO - 10.1002/pro.4137
M3 - Journal article
C2 - 34075639
AN - SCOPUS:85107377559
SN - 0961-8368
VL - 30
SP - 1854
EP - 1870
JO - Protein Science
JF - Protein Science
IS - 9
ER -