PXD024301 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Molecular basis of F-actin regulation and sarcomere assembly via myotilin |
Description | 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, 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 Zdiscs. |
HostingRepository | PRIDE |
AnnounceDate | 2021-02-22 |
AnnouncementXML | Submission_2021-02-22_04:16:27.668.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Friedel Drepper |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-02-22 03:48:32 | ID requested | |
⏵ 1 | 2021-02-22 04:16:28 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Sarcomeric Z-disc |
F-actin binding |
myotilin |
α-Actinin-2 |
integrative structural model of F-actin:myotilin |
competitive tropomyosin binding |
Z-disc-assembly regulation, cross-linking mass spectrometry, LC-MS/MS |
Contact List
Bettina Warscheid |
contact affiliation | Functional Proteomics Lab, Faculty of Biology, University of Freiburg, Germany |
contact email | bettina.warscheid@biologie.uni-freiburg.de |
lab head | |
Friedel Drepper |
contact affiliation | AG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany |
contact email | friedel.drepper@biologie.uni-freiburg.de |
dataset submitter | |
Full Dataset Link List
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024301
- Label: PRIDE project
- Name: Molecular basis of F-actin regulation and sarcomere assembly via myotilin