Journal
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
Volume 12, Issue 37, Pages 9026-9032Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpclett.1c02310
Keywords
-
Categories
Funding
- National Institutes of Health [GM-107703]
- National Science Foundation [CHE 19-00033]
- Welch Foundation [F-0019]
Ask authors/readers for more resources
Residues spanning distinct regions of the low-complexity domain of the FUS-LC RNA-binding protein form fibril structures with different core morphologies, S-bend for FUS-LC and U-bend for FUS-LC-C. The formation of core-1 is favored compared to core-2, and computer simulations suggest that the two fibril cores do not coexist.
Residues spanning distinct regions of the low-complexity domain of the RNA-binding protein, Fused in Sarcoma (FUS-LC), form fibril structures with different core morphologies. Solid-state NMR experiments show that the 214-residue FUS-LC forms a fibril with an S-bend (core-1, residues 39-95), while the rest of the protein is disordered. In contrast, the fibrils of the C-terminal variant (FUS-LC-C; residues 111-214) have a U-bend topology (core-2, residues 112-150). Absence of the U-bend in FUS-LC implies that the two fibril cores do not coexist. Computer simulations show that these perplexing findings could be understood in terms of the population of sparsely populated fibril-like excited states in the monomer. The propensity to form core-1 is higher compared to core-2. We predict that core-2 forms only in truncated variants that do not contain the core-1 sequence. At the monomer level, sequence-dependent enthalpic effects determine the relative stabilities of the core-1 and core-2 topologies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available