TY  - JOUR
AU  - Zielinski, Mara
AU  - Röder, Christine
AU  - Schröder, Gunnar F.
TI  - Challenges in sample preparation and structure determination of amyloids by cryo-EM
JO  - The journal of biological chemistry
VL  - 297
IS  - 2
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - FZJ-2021-05884
SP  - 100938 -
PY  - 2021
AB  - Amyloids share a common architecture but play disparate biological roles in processes ranging from bacterial defense mechanisms to protein misfolding diseases. Their structures are highly polymorphic, which makes them difficult to study by X-ray diffraction or NMR spectroscopy. Our understanding of amyloid structures is due in large part to recent advances in the field of cryo-EM, which allows for determining the polymorphs separately. In this review, we highlight the main stepping stones leading to the substantial number of high-resolution amyloid fibril structures known today as well as recent developments regarding automation and software in cryo-EM. We discuss that sample preparation should move closer to physiological conditions to understand how amyloid aggregation and disease are linked. We further highlight new approaches to address heterogeneity and polymorphism of amyloid fibrils in EM image processing and give an outlook to the upcoming challenges in researching the structural biology of amyloids.
LB  - PUB:(DE-HGF)16
C6  - pmid:34224730
UR  - <Go to ISI:>//WOS:000690871000008
DO  - DOI:10.1016/j.jbc.2021.100938
UR  - https://juser.fz-juelich.de/record/904314
ER  -