{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ryan VH"],"funding":["NIMH","Brown Institute for Brain Science","Office of Science of the U.S. Department of Energy","NIMH NIH HHS","Judith & Jean Pape Adams Charitable Foundation","ALS Association","U.S. Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), Division of Material Sciences and Engineering","NIGMS NIH HHS","NIGMS","National Science Foundation"],"pagination":["465-479.e7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5801700"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["69(3)"],"pubmed_abstract":["hnRNPA2, a component of RNA-processing membraneless organelles, forms inclusions when mutated in a syndrome characterized by the degeneration of neurons (bearing features of amyotrophic lateral sclerosis [ALS] and frontotemporal dementia), muscle, and bone. Here we provide a unified structural view of hnRNPA2 self-assembly, aggregation, and interaction and the distinct effects of small chemical changes-disease mutations and arginine methylation-on these assemblies. The hnRNPA2 low-complexity (LC) domain is compact and intrinsically disordered as a monomer, retaining predominant disorder in a liquid-liquid phase-separated form. Disease mutations D290V and P298L induce aggregation by enhancing and extending, respectively, the aggregation-prone region. Co-aggregating in disease inclusions, hnRNPA2 LC directly interacts with and induces phase separation of TDP-43. Conversely, arginine methylation reduces hnRNPA2 phase separation, disrupting arginine-mediated contacts. These results highlight the mechanistic role of specific LC domain interactions and modifications conserved across many hnRNP family members but altered by aggregation-causing pathological mutations."],"journal":["Molecular cell"],"pubmed_title":["Mechanistic View of hnRNPA2 Low-Complexity Domain Structure, Interactions, and Phase Separation Altered by Mutation and Arginine Methylation."],"pmcid":["PMC5801700"],"funding_grant_id":["17-IIP-342","DE-SC0013979","T32 GM007601","P20GM104937","R01GM118530","TG-MCB-120014","R01 GM118530","P20 GM104937","P30 GM122732","DE-AC02-05CH11231","T32MH020068","T32 MH020068","T32GM007601"],"pubmed_authors":["Zerze GH","Amaya J","Dignon GL","Chabata CV","Fawzi NL","Conicella AE","Silva R","Mittal J","Ryan VH","Burke KA"],"additional_accession":[]},"is_claimable":false,"name":"Mechanistic View of hnRNPA2 Low-Complexity Domain Structure, Interactions, and Phase Separation Altered by Mutation and Arginine Methylation.","description":"hnRNPA2, a component of RNA-processing membraneless organelles, forms inclusions when mutated in a syndrome characterized by the degeneration of neurons (bearing features of amyotrophic lateral sclerosis [ALS] and frontotemporal dementia), muscle, and bone. Here we provide a unified structural view of hnRNPA2 self-assembly, aggregation, and interaction and the distinct effects of small chemical changes-disease mutations and arginine methylation-on these assemblies. The hnRNPA2 low-complexity (LC) domain is compact and intrinsically disordered as a monomer, retaining predominant disorder in a liquid-liquid phase-separated form. Disease mutations D290V and P298L induce aggregation by enhancing and extending, respectively, the aggregation-prone region. Co-aggregating in disease inclusions, hnRNPA2 LC directly interacts with and induces phase separation of TDP-43. Conversely, arginine methylation reduces hnRNPA2 phase separation, disrupting arginine-mediated contacts. These results highlight the mechanistic role of specific LC domain interactions and modifications conserved across many hnRNP family members but altered by aggregation-causing pathological mutations.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Feb","modification":"2024-11-21T05:24:39.881Z","creation":"2019-03-26T22:50:05Z"},"accession":"S-EPMC5801700","cross_references":{"pubmed":["29358076"],"doi":["10.1016/j.molcel.2017.12.022"]}}