{"doi":"10.1016/j.jbc.2021.101194","title":"Prevalence and species distribution of the low-complexity, amyloid-like, reversible, kinked segment structural motif in amyloid-like fibrils","abstract":"Membraneless organelles (MLOs) are vital and dynamic reaction centers in cells that compartmentalize the cytoplasm in the absence of a membrane. Multivalent interactions between protein low-complexity domains contribute to MLO organization. Previously, we used computational methods to identify structural motifs termed low-complexity amyloid-like reversible kinked segments (LARKS) that promote phase transition to form hydrogels and that are common in human proteins that participate in MLOs. Here, we searched for LARKS in the proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli to gain an understanding of the distribution of LARKS in the proteomes of various species. We found that LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens but not in S. cerevisiae or P. falciparum. LARKS have high glycine content, which enables kinks to form as exemplified by the known LARKS-rich amyloidogenic structures of TDP43, FUS, and hnRNPA2, three proteins that are known to participate in MLOs. These results support the idea of LARKS as an evolved structural motif. Based on these results, we also established the LARKSdb Web server, which permits users to search for LARKS in their protein sequences of interest. Membraneless organelles (MLOs) are vital and dynamic reaction centers in cells that compartmentalize the cytoplasm in the absence of a membrane. Multivalent interactions between protein low-complexity domains contribute to MLO organization. Previously, we used computational methods to identify structural motifs termed low-complexity amyloid-like reversible kinked segments (LARKS) that promote phase transition to form hydrogels and that are common in human proteins that participate in MLOs. Here, we searched for LARKS in the proteomes of six model organisms: Homo sapiens, Drosophila melanogaster, Plasmodium falciparum, Saccharomyces cerevisiae, Mycobacterium tuberculosis, and Escherichia coli to gain an understanding of the distribution of LARKS in the proteomes of various species. We found that LARKS are abundant in M. tuberculosis, D. melanogaster, and H. sapiens but not in S. cerevisiae or P. falciparum. LARKS have high glycine content, which enables kinks to form as exemplified by the known LARKS-rich amyloidogenic structures of TDP43, FUS, and hnRNPA2, three proteins that are known to participate in MLOs. These results support the idea of LARKS as an evolved structural motif. Based on these results, we also established the LARKSdb Web server, which permits users to search for LARKS in their protein sequences of interest. A new area of cell biology is the study of membraneless organelles (MLOs) in the organization of cellular structures and metabolism. Many MLOs are RNA and protein assemblies that fulfill specific functions for the cell. Examples of MLOs in human cells include P bodies that degrade mRNA, stress granules (SGs) that store mRNA during stresses, and the nucleolus that processes rRNA. MLOs also function in other organisms such as germline P granules in Caenorhabditis elegans and SGs in yeast. The aforementioned organelles are not enveloped by membranes to partition them from the cytoplasm but instead organize through multivalent networks of homotypic and heterotypic reversible interactions between proteins and nucleic acids (1Alberti S. Gladfelter A. Mittag T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates.Cell. 2019; 176: 419-434Abstract Full Text Full Text PDF PubMed Scopus (681) Google Scholar, 2Li P. Banjade S. Cheng H.-C. Kim S. Chen B. Guo L. Llaguno M. Hollingsworth J.V. King D.S. Banani S.F. Russo P.S. Jiang Q.-X. Nixon B.T. Rosen M.K. Phase transitions in the assembly of multi-valent signaling proteins.Nature. 2012; 483: 336-340Crossref PubMed Scopus (1103) Google Scholar). These reversible networks allow MLOs to be dynamic. The","journal":"Journal of Biological Chemistry","year":2021,"id":158202,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":381282,"name":"Lukasz Goldschmidt","orcid":"0000-0002-2925-1159","position":1,"is_corresponding":false},{"id":225464,"name":"David Eisenberg","orcid":"0000-0003-2432-5419","position":2,"is_corresponding":false},{"id":250199,"name":"Michael P. Hughes","orcid":"0000-0002-6239-4151","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:44:26.210708Z","pmid":"34537246","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}