PXD006640-1

PXD006640 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis of amyloid corneal aggregates from lattice corneal dystrophy patients
Description	TGFBI associated Corneal Dystrophies (CD) are a group of inherited protein folding disorders linked to the mutation in the TGFBI gene. The resultant mutant protein (TGFBIp) is deposited as insoluble protein aggregates in various layers of the cornea leading to corneal opacity and poor vision. Depending on the type of mutation the deposits may be classified as amyloid fibrillar type, amorphous globular aggregates or a mixed form of both fibrils and amorphous aggregates. However, the molecular mechanism of the mutant-induced amyloidosis is not fully understood. This study aimsto characterize truncated peptides enriched in the amyloid aggregates and to identify the protein composition of the corneal aggregates derived from dystrophic patients using LC-MS/MS and compare the data with normal control cornea. We have identified several amyloid associated proteins, non-fibrillar amyloid associated proteins and TGFBIp as the major component of the corneal deposits. The results suggest that Apolipoprotein A-IV, Apolipoprotein E and Serine protease HtrA1 to be significantly enriched in the corneal deposits compared to the normal cornea. Comparative analysis of peptides from corneal deposits of patient and control identified several peptides of TGFBIp which are enriched in patient tissue and may form the core of corneal amyloids. Most of the peptides represent the 4th FAS-1 domain of the protein. Biophysical studies of two such peptides (G515DNRFSMLVAAIQSAGLTETLNR533 and Y571HIGDEILVSGGIGALVR588) demonstrate that they readily form amyloid fibrils under physiological conditions, confirming their intrinsic propensity to form amyloid fibrils. The identification of proteins which are involved in other protein misfolding disorders as well as identification of peptides from TGFBIp which form -amyloid core highlight that the mechanism of amyloid formation may share common molecular pathways.
HostingRepository	PRIDE
AnnounceDate	2022-02-28
AnnouncementXML	Submission_2022-02-28_02:33:22.677.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bamaprasad Dutta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-01 00:57:05	ID requested
⏵ 1	2022-02-28 02:33:23	announced
2	2023-11-14 08:49:09	announced	2023-11-14: Updated project metadata.

Venkatraman A, Dutta B, Murugan E, Piliang H, Lakshminaryanan R, Sook Yee AC, Pervushin KV, Sze SK, Mehta JS, Proteomic Analysis of Amyloid Corneal Aggregates from TGFBI-H626R Lattice Corneal Dystrophy Patient Implicates Serine-Protease HTRA1 in Mutation-Specific Pathogenesis of TGFBIp. J Proteome Res, 16(8):2899-2913(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Corneal Dystrophy, Lattice Corneal Dystrophy, TGFBI, TGFBIp, Amyloid fibrils, HtrA1, Apolipoprotein, Laser capture Microdissection

Siu Kwan SZE
contact affiliation	School of Biological Sciences Division of Structural Biology and Biochemistry Nanyang Technological University
contact email	sksze@ntu.edu.sg
lab head
Bamaprasad Dutta
contact affiliation	Nanyang Technological University
contact email	Bama0001@e.ntu.edu.sg
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/2022/02/PXD006640

PRIDE project URI

• PRIDE
  1. PXD006640
     1. Label: PRIDE project
     2. Name: Proteomics analysis of amyloid corneal aggregates from lattice corneal dystrophy patients