Project Details
Projekt
Cryo-EM structures of AL amyloid fibrils from human heart
Applicant
Professor Dr. Marcus Fändrich
Subject Area
Biochemistry
Term
from 2019 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 410477202
AL amyloid fibrils are key pathogenic agents in systemic AL amyloidosis. They are morphologically variable between different patients but little is known about their exact structures. For example, it is so far remained unclear whether different cases of cardiac amyloidosis involve similarly folded conformations or misfolded states of the fibril protein. Using AL amyloid fibril extracted from the explanted hearts of patients with a strong cardiac involvement we will address the following aims: (i) To extract Lambda-AL amyloid fibrils from cardiac amyloid deposits. (ii) To determine the cryo electron microscopy structure of a patient-derived AL amyloid fibril. (iii) To determine the structural diversity of Lambda-AL amyloid fibrils. (iv) To compare AL amyloid fibrils with light chain-derived amyloid-like fibrils. Through this work we will test the hypothesis that fibril formation in cardiac AL amyloidosis involves common structural themes for the assembly in vivo. Our work intends primarily to promote a better understanding of the molecular agents underlying systemic AL amyloidosis, the structural specifics of AL amyloid fibrils and their variability. Moreover, it will help us to further clarify the mechanism of fibril formation as it occur under natural conditions inside a patient.
DFG Programme
Research Units
