PXD027042-2

PXD027042 is an original dataset announced via ProteomeXchange.

Title	Expanding the Family of Extracellular Chaperones: Identification of Plasma Proteins with Chaperone Activity
Description	Proteostasis, the balance of protein synthesis, folding and degradation, is essential to maintain cellular function and viability, and the many known intracellular chaperones are recognised as playing key roles in sustaining life. In contrast, the identity of constitutively secreted extracellular chaperones (ECs) and their physiological roles in extracellular proteostasis is less completely understood. In the current study we designed and implemented a novel strategy to discover new ECs present in human blood. This strategy was based on the well-known propensity of chaperones to bind to regions of hydrophobicity exposed on misfolding proteins. We attached a destabilised protein that misfolds at 37 oC to magnetic beads, and used this as "bait" to bind to potential EC proteins. The bait-bearing beads were incubated in human serum for 2 h at either 37 oC or 4 oC (the latter serving as a control, not expected to induce bait protein misfolding). Proteins eluted from the beads were analysed by mass spectrometry to identify individual proteins and their relative abundance in eluates from beads incubated at 37 oC versus 4 oC. A group of proteins significantly more abundant in the eluate from the beads incubated at 37 oC were selected for in vitro analysis of chaperone activity. It was shown that vitronectin and plasminogen activator-3 inhibited both the in vitro aggregation of the Alzheimer's  peptide (Aβ1-42) to form fibrillar amyloid, and the aggregation of citrate synthase to form unstructured (amorphous) aggregates. In contrast, prothrombin, C1r, and C1s inhibited the aggregation of Aβ1-42 but did not inhibit citrate synthase aggregation. This study thus identified five novel and abundant putative ECs which may play important roles in the maintenance of extracellular proteostasis, and which apparently have differing abilities to inhibit the amorphous and amyloid-forming protein aggregation pathways.
HostingRepository	PRIDE
AnnounceDate	2021-09-24
AnnouncementXML	Submission_2021-09-23_22:43:04.040.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027042
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Albert Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-01 07:56:41	ID requested
1	2021-09-23 21:44:50	announced
⏵ 2	2021-09-23 22:43:04	announced	2021-09-24: Updated project metadata.

10.1002/PRO.4189;

Geraghty NJ, Satapathy S, Kelly M, Cheng F, Lee A, Wilson MR, Expanding the family of extracellular chaperones: Identification of human plasma proteins with chaperone activity. Protein Sci, 30(11):2272-2286(2021) [pubmed]

submitter keyword: Proteostasis, Plasminogen Activator Inhibitor 3,Extracellular Chaperones, C1s, C1r, Vitronectin, Prothrombin

Mark Wilson
contact affiliation	Illawarra Health and Medical Research Institute. Northfields Avenue, Wollongong. NSW. 2522. Australia.
contact email	mrw@uow.edu.au
lab head
Albert Lee
contact affiliation	Macquarie University
contact email	albert.lee@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027042
     1. Label: PRIDE project
     2. Name: Expanding the Family of Extracellular Chaperones: Identification of Plasma Proteins with Chaperone Activity