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PXD024301

PXD024301 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular basis of F-actin regulation and sarcomere assembly via myotilin
DescriptionSarcomeres, 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.
HostingRepositoryPRIDE
AnnounceDate2021-02-22
AnnouncementXMLSubmission_2021-02-22_04:16:27.668.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFriedel Drepper
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-02-22 03:48:32ID requested
12021-02-22 04:16:28announced
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 affiliationFunctional Proteomics Lab, Faculty of Biology, University of Freiburg, Germany
contact emailbettina.warscheid@biologie.uni-freiburg.de
lab head
Friedel Drepper
contact affiliationAG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany
contact emailfriedel.drepper@biologie.uni-freiburg.de
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
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