PXD011456

PXD011456 is an original dataset announced via ProteomeXchange.

Title	Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome
Description	Most natural proteins fold into a native conformation stabilized by non-covalent interactions. The energy difference between native and denatured states (Gfolding) is highly variable between proteins and can range from less than -10 kcal per mole for highly stable proteins to positive values for intrinsically disordered proteins. Folding stability is a dynamic property of proteins and can be modulated by molecular chaperones and binding interactions. The stability of a protein influences its tendency to aggregate, degrade or become covalently modified in cells. Despite its significance to understanding protein folding and function, quantitative analyses of thermodynamic stability have been mostly limited to small soluble proteins in purified systems. Here, we have used a highly multiplexed bottom-up proteomics approach, based on analyses of rates of methionine oxidation, to quantify the thermodynamic stabilities of the human proteome in crude extracts obtained from dermal fibroblasts. Our data provide structural and stability information for more than 10,000 unique regions and domains within more than 3,200 proteins. The data identifies lysosomal and extracellular proteins as the most stable ontological subsets of the proteome. We show that the stability of proteins can impact their tendency to become oxidized and are globally altered by the osmolyte trimethylamine-N-oxide (TMAO). We also show that most proteins designated as IDPs retain their unfolded structure in the complex milieu of the cell and most cannot be refolded by TMAO. Together, the data provide a census of the stability of the human proteome and validate a methodology for global analysis of protein thermodynamic stabilities.
HostingRepository	PRIDE
AnnounceDate	2019-03-12
AnnouncementXML	Submission_2019-03-12_03:18:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ethan Walker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-23 05:45:02	ID requested
1	2018-11-21 03:55:07	announced
2	2019-03-12 03:03:20	announced	Updated publication reference for PubMed record(s): 30846556.
⏵ 3	2019-03-12 03:18:55	announced	Updated project metadata.

Walker EJ, Bettinger JQ, Welle KA, Hryhorenko JR, Ghaemmaghami S, Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome. Proc Natl Acad Sci U S A, 116(13):6081-6090(2019) [pubmed]

curator keyword: Biological

submitter keyword: Human, protein stability, protein folding, quantitative proteomics, methionine oxidation, Lumos

Sina Ghaemmaghami
contact affiliation	Associate professor, department of Biology. University of Rochester,NY, USA University of Rochester Mass Spectrometry Resource Laboratory, NY, USA (lab head)
contact email	sghaemma@ur.rochester.edu
lab head
Ethan Walker
contact affiliation	University of Rochester
contact email	Ethan_walker@urmc.rochester.edu
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/2018/11/PXD011456

PRIDE project URI

• PRIDE
  1. PXD011456
     1. Label: PRIDE project
     2. Name: Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome