Molecular interactions of FG nucleoporin repeats at high resolution.
Nat Chem
; 14(11): 1278-1285, 2022 11.
Article
in En
| MEDLINE
| ID: mdl-36138110
Proteins that contain repeat phenylalanine-glycine (FG) residues phase separate into oncogenic transcription factor condensates in malignant leukaemias, form the permeability barrier of the nuclear pore complex and mislocalize in neurodegenerative diseases. Insights into the molecular interactions of FG-repeat nucleoporins have, however, remained largely elusive. Using a combination of NMR spectroscopy and cryoelectron microscopy, we have identified uniformly spaced segments of transient ß-structure and a stable preformed α-helix recognized by messenger RNA export factors in the FG-repeat domain of human nucleoporin 98 (Nup98). In addition, we have determined at high resolution the molecular organization of reversible FG-FG interactions in amyloid fibrils formed by a highly aggregation-prone segment in Nup98. We have further demonstrated that amyloid-like aggregates of the FG-repeat domain of Nup98 have low stability and are reversible. Our results provide critical insights into the molecular interactions underlying the self-association and phase separation of FG-repeat nucleoporins in physiological and pathological cell activities.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Pore
/
Nuclear Pore Complex Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Chem
Journal subject:
QUIMICA
Year:
2022
Document type:
Article
Affiliation country:
Germany
Country of publication:
United kingdom