Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950315093> ?p ?o ?g. }
- W2950315093 endingPage "e3000327" @default.
- W2950315093 startingPage "e3000327" @default.
- W2950315093 abstract "526-residue Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) for its functions, which can further transit into pathological aggregation. ATP and nucleic acids, the universal cellular actors, were shown to modulate LLPS of FUS in a unique manner: enhancement and then dissolution. Currently, the driving force for LLPS of FUS is still under debate, while the mechanism for the modulation remains completely undefined. Here, by NMR and differential interference contrast (DIC) imaging, we characterized conformations, dynamics, and LLPS of FUS and its domains and subsequently their molecular interactions with oligonucleic acids, including one RNA and two single-stranded DNA (ssDNA) molecules, as well as ATP, Adenosine monophosphate (AMP), and adenosine. The results reveal 1) both a prion-like domain (PLD) rich in Tyr but absent of Arg/Lys and a C-terminal domain (CTD) abundant in Arg/Lys fail to phase separate. By contrast, the entire N-terminal domain (NTD) containing the PLD and an Arg-Gly (RG)-rich region efficiently phase separate, indicating that the π-cation interaction is the major driving force; 2) despite manifesting distinctive NMR observations, ATP has been characterized to modulate LLPS by specific binding as oligonucleic acids but with much lower affinity. Our results together establish a unified mechanism in which the π-cation interaction acts as the major driving force for LLPS of FUS and also serves as the target for modulation by ATP and oligonucleic acids through specific binding. This mechanism predicts that a myriad of proteins unrelated to RNA-binding proteins (RBPs) but with Arg/Lys-rich disordered regions could be modulated by ATP and nucleic acids, thus rationalizing the pathological association of Amyotrophic lateral sclerosis (ALS)-causing C9ORF72 dipeptides with any nucleic acids to manifest cytotoxicity." @default.
- W2950315093 created "2019-06-27" @default.
- W2950315093 creator A5038512105 @default.
- W2950315093 creator A5046217738 @default.
- W2950315093 creator A5073125119 @default.
- W2950315093 creator A5085544895 @default.
- W2950315093 date "2019-06-12" @default.
- W2950315093 modified "2023-09-29" @default.
- W2950315093 title "A unified mechanism for LLPS of ALS/FTLD-causing FUS as well as its modulation by ATP and oligonucleic acids" @default.
- W2950315093 cites W118988577 @default.
- W2950315093 cites W1729426031 @default.
- W2950315093 cites W1789215739 @default.
- W2950315093 cites W1938908576 @default.
- W2950315093 cites W1941145541 @default.
- W2950315093 cites W1952608303 @default.
- W2950315093 cites W1963826942 @default.
- W2950315093 cites W1979123965 @default.
- W2950315093 cites W1988624456 @default.
- W2950315093 cites W1993084790 @default.
- W2950315093 cites W1993877983 @default.
- W2950315093 cites W2006322736 @default.
- W2950315093 cites W2008386999 @default.
- W2950315093 cites W2011387974 @default.
- W2950315093 cites W2019345165 @default.
- W2950315093 cites W2026226960 @default.
- W2950315093 cites W2040417365 @default.
- W2950315093 cites W2051168928 @default.
- W2950315093 cites W2053202752 @default.
- W2950315093 cites W2054352933 @default.
- W2950315093 cites W2059707627 @default.
- W2950315093 cites W2067254074 @default.
- W2950315093 cites W2073073462 @default.
- W2950315093 cites W2074706587 @default.
- W2950315093 cites W2074898096 @default.
- W2950315093 cites W2075185862 @default.
- W2950315093 cites W2076098023 @default.
- W2950315093 cites W2079712877 @default.
- W2950315093 cites W2080786759 @default.
- W2950315093 cites W2082176639 @default.
- W2950315093 cites W2087546428 @default.
- W2950315093 cites W2097630727 @default.
- W2950315093 cites W2103336074 @default.
- W2950315093 cites W2104017463 @default.
- W2950315093 cites W2109835272 @default.
- W2950315093 cites W2112597123 @default.
- W2950315093 cites W2112714817 @default.
- W2950315093 cites W2117569373 @default.
- W2950315093 cites W2137453899 @default.
- W2950315093 cites W2137474088 @default.
- W2950315093 cites W2139066576 @default.
- W2950315093 cites W2146926661 @default.
- W2950315093 cites W2149314663 @default.
- W2950315093 cites W2150860983 @default.
- W2950315093 cites W2156771958 @default.
- W2950315093 cites W2159354359 @default.
- W2950315093 cites W2159795894 @default.
- W2950315093 cites W2164245070 @default.
- W2950315093 cites W2168958678 @default.
- W2950315093 cites W2169821755 @default.
- W2950315093 cites W2172179321 @default.
- W2950315093 cites W2228446732 @default.
- W2950315093 cites W2313097851 @default.
- W2950315093 cites W2333448697 @default.
- W2950315093 cites W2402791934 @default.
- W2950315093 cites W2480300184 @default.
- W2950315093 cites W2509948508 @default.
- W2950315093 cites W2533664860 @default.
- W2950315093 cites W2534922319 @default.
- W2950315093 cites W2556818673 @default.
- W2950315093 cites W2593868122 @default.
- W2950315093 cites W2595869676 @default.
- W2950315093 cites W2604909829 @default.
- W2950315093 cites W2607272486 @default.
- W2950315093 cites W2614819858 @default.
- W2950315093 cites W2615607456 @default.
- W2950315093 cites W2619839156 @default.
- W2950315093 cites W2742396220 @default.
- W2950315093 cites W2749472324 @default.
- W2950315093 cites W2756821926 @default.
- W2950315093 cites W2758396775 @default.
- W2950315093 cites W2769128215 @default.
- W2950315093 cites W2784297130 @default.
- W2950315093 cites W2785329615 @default.
- W2950315093 cites W2793647943 @default.
- W2950315093 cites W2794654572 @default.
- W2950315093 cites W2797600975 @default.
- W2950315093 cites W2800374982 @default.
- W2950315093 cites W2801356113 @default.
- W2950315093 cites W2801688422 @default.
- W2950315093 cites W2802667264 @default.
- W2950315093 cites W2802842075 @default.
- W2950315093 cites W2803517261 @default.
- W2950315093 cites W2808121690 @default.
- W2950315093 cites W2810866092 @default.
- W2950315093 cites W2884082692 @default.
- W2950315093 cites W2891026974 @default.
- W2950315093 cites W2893049312 @default.
- W2950315093 cites W2899020985 @default.