PXD045520-1

PXD045520 is an original dataset announced via ProteomeXchange.

Title	hydrogen deuterium uptake comparison between wild-type, I499F, and D380A variants of the myocilin olfactomedin domain
Description	Studies of folded-to-misfolded transitions using model protein systems reveal a range of unfolding needed for exposure of amyloid-prone regions for subsequent fibrillization. Here, we probe the relationship between unfolding and aggregation for glaucoma-associated myocilin. Mutations within the olfactomedin domain of myocilin (OLF) cause a gain-of-function, namely cytotoxic intracellular aggregation, which hastens disease progression. Aggregation by wild-type OLF (OLFWT) competes with its chemical unfolding, but only below the threshold where OLF loses tertiary structure. Representative moderate (OLFD380A) and severe (OLFI499F) disease variants aggregate differently, with rates comparable to OLFWT in initial stages of unfolding, and variants adopt distinct partially folded structures seen along the OLFWT urea-unfolding pathway. Whether initiated with mutation or chemical perturbation, unfolding propagates outward to the propeller surface. In sum, for this large protein prone to amyloid formation, the requirement for a conformational change to promote amyloid fibrillization leads to direct competition between unfolding and aggregation.
HostingRepository	PRIDE
AnnounceDate	2023-11-27
AnnouncementXML	Submission_2023-11-27_15:00:44.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Minh Thu Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	ACQUITY UPLC

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-20 06:14:39	ID requested
⏵ 1	2023-11-27 15:00:45	announced

Dataset with its publication pending

submitter keyword: dynamics, glaucoma,myocilin

Raquel L Lieberman
contact affiliation	School of Chemistry & Biochemistry Georgia Institute of Technology 901 Atlantic Dr. NW Atlanta, GA 30332
contact email	raquel.lieberman@chemistry.gatech.edu
lab head
Minh Thu Ma
contact affiliation	Georgia Institute of Technology
contact email	mma23@gatech.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/2023/11/PXD045520

PRIDE project URI

• PRIDE
  1. PXD045520
     1. Label: PRIDE project
     2. Name: hydrogen deuterium uptake comparison between wild-type, I499F, and D380A variants of the myocilin olfactomedin domain