PXD001282

PXD001282 is an original dataset announced via ProteomeXchange.

Title	Differential N-terminal COFRADIc analyses of Ogden fibroblasts
Description	The X-linked lethal Ogden syndrome was the first reported human genetic disorder associated with a mutation in an N-terminal acetyltransferase gene. The affected males harbour a Ser37Pro mutation in the gene encoding hNaa10, the catalytic subunit of NatA, themajor human NAT. In order to understand the detrimental impact of hNaa10 Ser37Pro, we performed structural, molecular and cellular investigations. Structural models and molecular dynamics simulations of the human NatA and its Ser37Pro mutant suggest differences in regions involved in catalysis and at the interface between hNaa10 and the auxiliary subunit hNaa15. In agreement, biochemical data demonstrate a reduced catalytic capacity and an impaired NatA complex formation with hNaa10 Ser37Pro. Patient derived Naa10 mutant cells show reduced Nt-acetylation for a subset of NatA/NatE-type substrates compared to wild type Naa10 cells. Ogden syndrome fibroblasts further display abnormal cell proliferation and migration capacity, possibly linked to perturbed Retinoblastoma- and MYLK-pathways, respectively. Differential N-terminal combined fractional diagonal chromatography (COFRADIC) was used to quantify the degree and define the patterns of in vivo protein Nt-acetylation and here used to investigate whether patient cells derived from an affected Ogden male (carrying the Naa10 S37P mutation) displayed altered levels of protein Nt-acetylation at the proteome-wide level.
HostingRepository	PRIDE
AnnounceDate	2016-04-12
AnnouncementXML	Submission_2016-04-12_04:26:20.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD001282
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Line Merethe Myklebust
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide - site C: 57.021464; 6x(13)C: 4x(15)N labeled L-arginine; 2-pyrrolidone-5-carboxylic acid (Gln): -17.026549; monohydroxylated residue: 15.994915; isotope labeled residue; N-acetylated residue: 42.010565
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-09-03 05:43:15	ID requested
⏵ 1	2016-04-12 04:26:21	announced

Myklebust LM, Van Damme P, St, ø, ve SI, D, ö, rfel MJ, Abboud A, Kalvik TV, Grauffel C, Jonckheere V, Wu Y, Swensen J, Kaasa H, Liszczak G, Marmorstein R, Reuter N, Lyon GJ, Gevaert K, Arnesen T, Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects. Hum Mol Genet, 24(7):1956-76(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, fibroblasts, Naa10 S37P mutation, N-terminal acetylation, Differential COFRADIC, LC-MS/MS

Line Merethe Myklebust
contact affiliation	Dr.
contact email	Line.Myklebust@mbi.uib.no
lab head
Line Merethe Myklebust
contact affiliation	University of Bergen
contact email	Line.Myklebust@mbi.uib.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD001282
     1. Label: PRIDE project
     2. Name: Differential N-terminal COFRADIc analyses of Ogden fibroblasts