Abstract
Membraneless Organelles (MLOs) are vital and dynamic reaction centers in cells that organize metabolism in the absence of a membrane. Multivalent interactions between protein Low-Complexity Domains (LCDs) contribute to MLO organization. Our previous work used computational methods to identify structural motifs termed Low-complexity Amyloid-like Reversible Kinked Segments (LARKS) that can phase-transition to form hydrogels and are common in human proteins that participate in MLOs. Here we searched for LARKS in proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli. We find LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens, but not in S. cerevisiae or P. falciparum. Abundant LARKS require high glycine content, which enables kinks to form in LARKS as is illustrated in the known LARKS-rich amyloid structures of TDP43, FUS, and hnRNPA2, three proteins that participate in MLOs. These results support the idea of LARKS as an evolved structural motif and we offer the LARKSdb webserver which permits users to search for LARKS in their protein sequences of interest.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Abbreviations
- LARKS
- Low Complexity, Amyloid-like Reversible Kinked Segments
- LCDs
- Low-Complexity Domains
- PrLDs
- Prion-like Domains
- IDRs
- Intrinsically Disordered Regions
- LLPS
- Liquid-Liquid Phase Separation
- MLOs
- Membraneless Organelles
- LARKS∩LCD protein
- protein that has at least one LCD and for which the fraction of LARKS is greater than average for its proteome
- LARKS∩LCD residue
- an amino acid residue that is a predicted LARKS within a LCD