PXD024301-1

PXD024301 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-22 03:48:32	ID requested
⏵ 1	2021-02-22 04:16:28	announced

Dataset with its publication pending

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

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/02/PXD024301

PRIDE project URI

• PRIDE
  1. PXD024301
     1. Label: PRIDE project
     2. Name: Molecular basis of F-actin regulation and sarcomere assembly via myotilin