PXD008337

PXD008337 is an original dataset announced via ProteomeXchange.

Title	Lamin A dimer and tetramer cross-links help explain disease mutations and polymer plasticity
Description	Lamins are intermediate filament proteins responsible for nuclear mechanical integrity. Though linked to multiple heritable diseases, lamin structure and that of other intermediate filaments remains elusive. We employed cross-linking mass spectrometry to gain structural insights into lamin A dimer and tetramer structure. While confirming the parallel coiled-coil rod, we report that, contrary to prediction, rod linker regions are highly flexible and compressible. This explains the recently reported rod shortening in the assembled polymer and aspects of intermediate filament stretch properties. We further elucidate an extended interface in lamin A tetramers where both head and tail unstructured regions flanking the rod of each dimer act as polar bridges to stabilize lamin head-to-tail assembly. Furthermore, changes in these regions between dimer and tetramer forms suggest an ordered polymer assembly. Importantly, several residues mutated in laminopathies disrupt this interface and impair assembly, potentially explaining their role in disease.
HostingRepository	PRIDE
AnnounceDate	2019-07-12
AnnouncementXML	Submission_2019-07-16_01:59:26.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juan Zou
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	isotope labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-30 01:19:07	ID requested
1	2019-07-12 03:56:54	announced
⏵ 2	2019-07-16 01:59:27	announced	Updated publication reference for PubMed record(s): 31296869.

Makarov AA, Zou J, Houston DR, Spanos C, Solovyova AS, Cardenal-Peralta C, Rappsilber J, Schirmer EC, Lamin A molecular compression and sliding as mechanisms behind nucleoskeleton elasticity. Nat Commun, 10(1):3056(2019) [pubmed]

curator keyword: Biological

submitter keyword: Lamin A, Cross-link Mass Spectrometry, SILAC, EM

Prof. Juri Rappsilber
contact affiliation	Wellcome Centre for Cell Biology, University of Edinburgh,Max Born Crescent, Edinburgh, EH9 3BF, UK
contact email	juri.rappsilber@ed.ac.uk
lab head
Juan Zou
contact affiliation	The University of Edinburgh
contact email	jzou@ed.ac.uk
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/2019/07/PXD008337

PRIDE project URI

• PRIDE
  1. PXD008337
     1. Label: PRIDE project
     2. Name: Lamin A dimer and tetramer cross-links help explain disease mutations and polymer plasticity