S Gs contain mainly non - translating mRNAs and RNA - binding proteins as well as additional proteins affecting their functions 3,13 18.
Does Not Enable Window Maker Tf2 Download File PDFDownload file PDF Download file PDF Read file Download citation Copy link Link copied Read file Download citation Copy link Link copied References (71) Figures (3) Abstract and Figures G3BP is the central hub within the protein-RNA interaction network of stress-induced bio-molecular condensates known as stress granules (SG).The SG-associated proteins Caprin-1 and USP10 exhibit mutually exclusive binding to the structured NTF2-domain of G3BP1, thereby regulating G3BP1-mediated condensation, but with opposite effects: Caprin-1 promotes but USP10 inhibits SG formation.Herein, we present the crystal structure of G3BP1-NTF2 in complex with a Caprin-1 derived short linear motif (SLiM), which provides a molecular understanding for the mutually exclusive binding of USP10 and Caprin-1 to G3BP1.
G3BP1Caprin-1 interactions disrupted via point mutations resulted in fewer and smaller SG condensates. In addition, biochemical binding assays demonstrated reduced binding of Caprin-1 to G3BP1 at lower pH values. YNFI(Q)-and FGDF cover the same NTF2 binding site, but only Caprin-1 356-386 extends to a third site between helices 2 and 3 NTF2-His31 mutants form fewer stress granules with reduced Caprin-1 content (A) Representative microscopy images of G3BP12 U2OS cells stably expressing indicated G3BP1-wildtype, -H31A, -H62A and -Q58E were stressed with sodium arsenite (200 M) for 1h and compared to non-stressed (mock) cells. Figure S2 The asymmetric unit contains three NTF2 dimers and two 20AA-long and 4AA-short fragments of Caprin-1 356-386 bound to chains D and F (A) The asymmetric unit of the G3BP1-NTF2 Caprin-1 356-386 crystal structure contains three nonidentical NTF2-dimers created by chains CD, AE and BF. The 20AA-long and 4AA-short Caprin-1 fragments bound to NTF2 chains D and F, respectively. B) The discovery and refined maps as well as the built model of Phe-372 and few additional backbone atoms of Caprin-1 356-386 bound to chain F are visualized similarly to the long Caprin-1 356-386 fragment in Figure 1B. Figures - uploaded by Marc D Panas Author content All figure content in this area was uploaded by Marc D Panas Content may be subject to copyright. Does Not Enable Window Maker Tf2 For Free Public FullDoes Not Enable Window Maker Tf2 Free Public FullDiscover the worlds research 20 million members 135 million publications 700k research projects Join for free Public Full-texts 2 21-02-05, Caprin1G3BP ms, bi oArxiv.pdf Content available from CC BY-NC-ND 4.0: 21-02-05, Caprin1G3BP ms, bioArxiv.pdf Caprin-1 binding to the critical stress granule protein G3BP1 is regulated by pH.pdf Content uploaded by Marc D Panas Author content All content in this area was uploaded by Marc D Panas on Feb 09, 2021 Content may be subject to copyright. Caprin-1 binding to the critical stress granule protein G3BP1 is regulated by pH.pdf Content available from CC BY-NC-ND 4.0: 21-02-05, Caprin1G3BP ms, bioArxiv.pdf Caprin-1 binding to the critical stress granule protein G3BP1 is regulated by pH.pdf Available via license: CC BY-NC-ND 4.0 Content may be subject to copyright. Panas 2, Lucy Williams 2, N ancy Kedersha 3, Jonas S imon Fleck 1, Timothy J.C. Tan 2, Anders Olsson 4, Ainhoa Mol iner Morro 2, Leo Hanke 2, Joh an Nilveb rant 5, Kim Anh Giang 5, Per - ke Nygren 5, Paul Anderson 3, Adnane Achour 1, Ge rald M. The SG - associated proteins Caprin - 1 and USP10 exhibit mutually exclusive binding to the structured NTF2 - domain of G3BP1, thereby regulating G3BP1 - mediated condensation, but with opposi te effects: Caprin - 1 promotes but USP10 inhibits SG formation. Herein, we present the crystal structure of G 3BP1 - NTF2 in co mplex with a Capri n - 1 derived short linear motif (SLiM), which provid es a molecular understanding for the mu tually exclusive binding of USP10 and Caprin - 1 to G3BP1. Caprin - 1 but not USP10 contacts t wo G3BP1 - NTF2 histidine residues, which was confirmed using biochemical, biophysical and cellular biological binding assays. G3BP1Caprin - 1 interactions disr upted via point mutations resulted in fewer and smaller SG condensates. In addition, biochemical binding assays demonstrated reduced binding of Caprin - 1 to G3BP1 at lower pH values. Finally, ratiometric pH sensitive measurements of SGs revealed a substantial drop in pH compared to the adja cent cytosol, suggesting that reduc ed pH c an fine - tune and regulate the G3BP1 - mediated interaction network via a NTF2 - mediated pH - sensitive SLiM - selection mechanism. It is made available under a preprint (which was not certified by peer review) is the authorfunder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted February 5, 2021.; doi: bioRxiv preprint. D ysregulat ed SGs are found in various diseases including cancer, viral infections and neurodegeneration 48. The com position and conc entrations of SG components are evolutionarily shaped to separate in to a condensed phase upon stress and their partitioning follows basic thermodynamic principles 10 12.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |