PXD045520 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-20 06:14:39 | ID requested | |
⏵ 1 | 2023-11-27 15:00:45 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: dynamics, glaucoma,myocilin |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045520
- Label: PRIDE project
- Name: hydrogen deuterium uptake comparison between wild-type, I499F, and D380A variants of the myocilin olfactomedin domain