PXD012427

PXD012427 is an original dataset announced via ProteomeXchange.

Title	Altered Domain Structure of the Prion Protein Caused by Cu2+ Binding and Functionally Relevant Mutations: Analysis by Cross‐Linking, MS/MS, and NMR
Description	The endogenous cellular prion protein (PrPC) can misfold into the scrapie isoform (PrPSc) and cause fatal infectious diseases. Despite significant research on the prion protein, both its normal function and whether alterations to that function play a critical role in prion diseases remain unknown. The protein consists of a predominantly alpha-helical C-terminal domain and an unstructured N-terminal domain that can coordinate Cu2+. Previous studies using NMR and EPR have revealed a tertiary association between the N-terminal domain and the C-terminal domain that we have hypothesized to be critical to the protein’s normal function. Here we investigated and quantified the inter-domain interactions within three different prion variants (wild type recombinant mouse PrPC, mutant delta central region (ΔCR), and disease mutant (E199K) after chemical cross-linking with a newly designed MS-cleavable reagent 1-(4-((2,5-Dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-4-(2-(3-methyl-3H-diazirin-3-yl)ethyl)-1,4-diazabicyclo[2.2.2] octane-1,4-diium (APDC4), followed by nHPLC(RP) and tandem MS analysis.
HostingRepository	PRIDE
AnnounceDate	2020-06-16
AnnouncementXML	Submission_2020-06-16_01:04:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Catherine Costello
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2019-01-18 03:45:57	ID requested
⏵ 1	2020-06-16 01:04:19	announced

McDonald AJ, Leon DR, Markham KA, Wu B, Heckendorf CF, Schilling K, Showalter HD, Andrews PC, McComb ME, Pushie MJ, Costello CE, Millhauser GL, Harris DA, Binding and Functionally Relevant Mutations: Analysis by Cross-Linking, MS/MS, and NMR. Structure, 27(6):907-922.e5(2019) [pubmed]

curator keyword: Biological

submitter keyword: Prion, cross-linking, mass spectrometry, inter-domain protein interaction

Catherine E. Costello
contact affiliation	Boston University School of Medicine Center for Biomedical Mass Spectrometry
contact email	cecmsms@bu.edu
lab head
Catherine Costello
contact affiliation	Boston Univ School of Medicine
contact email	CECMSMS@BU.EDU
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012427
     1. Label: PRIDE project
     2. Name: Altered Domain Structure of the Prion Protein Caused by Cu2+ Binding and Functionally Relevant Mutations: Analysis by Cross‐Linking, MS/MS, and NMR