RT Journal Article
SR Electronic
T1 The prevalence and distribution in genomes of low-complexity, amyloid-like, reversible, kinked segment (LARKS), a common structural motif in amyloid-like fibrils
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.08.415679
DO 10.1101/2020.12.08.415679
A1 Hughes, Michael P.
A1 Goldschmidt, Luki
A1 Eisenberg, David S.
YR 2020
UL http://biorxiv.org/content/early/2020/12/08/2020.12.08.415679.abstract
AB 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 StatementThe authors have declared no competing interest.LARKSLow Complexity, Amyloid-like Reversible Kinked SegmentsLCDsLow-Complexity DomainsPrLDsPrion-like DomainsIDRsIntrinsically Disordered RegionsLLPSLiquid-Liquid Phase SeparationMLOsMembraneless OrganellesLARKS∩LCD proteinprotein that has at least one LCD and for which the fraction of LARKS is greater than average for its proteomeLARKS∩LCD residuean amino acid residue that is a predicted LARKS within a LCD