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| 001 | 471053 | ||
| 005 | 20250724175801.0 | ||
| 024 | 7 | _ | |a 10.1371/journal.pbio.3001148 |2 doi |
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| 100 | 1 | _ | |a Kostan, Julius |0 P:(DE-H253)PIP1019431 |b 0 |
| 245 | _ | _ | |a Molecular basis of F-actin regulation and sarcomere assembly via myotilin |
| 260 | _ | _ | |a Lawrence, KS |c 2021 |b PLoS |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a Sarcomeres, the basic contractile units of striated muscle cells, contain arrays of thin (actin) and thick (myosin) filaments that slide past each other during contraction. The Ig-like domain-containing protein myotilin provides structural integrity to Z-discs—the boundaries between adjacent sarcomeres. Myotilin binds to Z-disc components, including F-actin and α-actinin-2, but the molecular mechanism of binding and implications of these interactions on Z-disc integrity are still elusive. To illuminate them, we used a combination of small-angle X-ray scattering, cross-linking mass spectrometry, and biochemical and molecular biophysics approaches. We discovered that myotilin displays conformational ensembles in solution. We generated a structural model of the F-actin:myotilin complex that revealed how myotilin interacts with and stabilizes F-actin via its Ig-like domains and flanking regions. Mutant myotilin designed with impaired F-actin binding showed increased dynamics in cells. Structural analyses and competition assays uncovered that myotilin displaces tropomyosin from F-actin. Our findings suggest a novel role of myotilin as a co-organizer of Z-disc assembly and advance our mechanistic understanding of myotilin’s structural role in Z-discs. |
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| 700 | 1 | _ | |a Pavšič, Miha |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Puž, Vid |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Schwarz, Thomas C. |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Drepper, Friedel |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Molt, Sibylle |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Gräwert, Melissa Ann |0 P:(DE-H253)PIP1016308 |b 6 |
| 700 | 1 | _ | |a Schreiner, Claudia |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Sajko, Sara |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a van der Ven, Peter F. M. |0 P:(DE-HGF)0 |b 9 |
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| 700 | 1 | _ | |a Svergun, Dmitri I. |0 P:(DE-H253)PIP1001422 |b 11 |
| 700 | 1 | _ | |a Warscheid, Bettina |0 P:(DE-HGF)0 |b 12 |
| 700 | 1 | _ | |a Konrat, Robert |0 P:(DE-HGF)0 |b 13 |
| 700 | 1 | _ | |a Fürst, Dieter O. |0 P:(DE-HGF)0 |b 14 |
| 700 | 1 | _ | |a Lenarcic, Brigita |0 P:(DE-H253)PIP1095129 |b 15 |e Corresponding author |
| 700 | 1 | _ | |a Djinović-Carugo, Kristina |0 P:(DE-HGF)0 |b 16 |e Corresponding author |
| 773 | _ | _ | |a 10.1371/journal.pbio.3001148 |g Vol. 19, no. 4, p. e3001148 - |0 PERI:(DE-600)2126773-X |n 4 |p e3001148 (1-34) |t PLoS biology |v 19 |y 2021 |x 1545-7885 |
| 856 | 4 | _ | |u https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001148 |
| 856 | 4 | _ | |u https://bib-pubdb1.desy.de/record/471053/files/Molecular%20basis%20of%20F%20actin%20regulation%20and%20sarcomere%20assembly%20via%20myotilin.pdf |y OpenAccess |
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