PXD035049-2

PXD035049 is an original dataset announced via ProteomeXchange.

Title	Aggrelyte-2 Promotes Protein Solubility and Decreases Stiffness in Lenses through Lysine Acetylation and Disulfide Reduction
Description	Aging proteins in the lens become increasingly aggregated and insoluble, contributing to presbyopia. In this study, we investigated the ability of aggrelyte-2 (N,S-Diacetyl-L-cysteine methyl ester) to reverse the water insolubility of aged human lens proteins and to decrease stiffness in cultured human and rodent lenses. Aggrelyte-2 was incubated (500 µM) with water-insoluble proteins of aged human lenses (65-75 years) for 24 or 48 h. A control compound that lacked an S-acetyl group (aggrelyte-2C) was also tested. We observed 19-30% solubility of WI upon the treatment with aggrelyte-2. Aggrelyte-2C also increased protein solubility, but its effect was approximately 1.4-fold lower than that of aggrelyte-2. The protein thiol contents were 1.9 to 4.9-fold higher in the aggrelyte-treated samples than in the untreated samples. The LC-MS/MS results showed N-acetyllysine (AcK) levels of 1.5 to 2.1 nmoles/mg protein and 0.6 to 0.9 nmoles/mg protein in the aggrelyte-2- and aggrelyte-2C-treated samples, respectively. Mouse (C57BL/6J) lenses (incubated for 24 h) and human lenses (incubated for 72 h) with 1.0 mM aggrelyte-2 showed significant decreases in stiffness with simultaneous increases in soluble proteins (human lenses) and protein-AcK levels and such changes were not observed in aggrelyte-2C treated lenses. Mass spectrometry of the solubilized protein revealed AcK in all crystallins but more in α-crystallins. These results suggest that aggrelyte-2 increases protein solubility and decreases lens stiffness through acetylation and disulfide reduction. Aggrelyte-2 might be useful in treating presbyopia in humans.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:45:24.729.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cole Michel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	6520A Quadrupole Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-30 07:47:29	ID requested
1	2024-10-08 11:37:05	announced
⏵ 2	2024-10-22 05:45:28	announced	2024-10-22: Updated project metadata.

10.1111/acel.13797;

Panja S, Nahomi RB, Rankenberg J, Michel CR, Gaikwad H, Nam MH, Nagaraj RH, Aggrelyte-2 promotes protein solubility and decreases lens stiffness through lysine acetylation and disulfide reduction: Implications for treating presbyopia. Aging Cell, 22(4):e13797(2023) [pubmed]

ProteomeXchange project tag: EyeOME (B/D-HPP), Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Human, PTM, Lens, Lysine, Eye, Acetylation

Cole Michel
contact affiliation	University of Colorado Skaggs School of Pharmacy
contact email	cole.michel@cuanschutz.edu
lab head
Cole Michel
contact affiliation	Univeristy of Colorado - Skaggs School of Pharmacy
contact email	cole.michel@cuanschutz.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035049
     1. Label: PRIDE project
     2. Name: Aggrelyte-2 Promotes Protein Solubility and Decreases Stiffness in Lenses through Lysine Acetylation and Disulfide Reduction