PXD034046

PXD034046 is an original dataset announced via ProteomeXchange.

Title	Synthetic antibody-derived immunopeptide provides neuroprotection in glaucoma through molecular interaction with retinal protein Histone H3.1
Description	Glaucoma is a group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs) as well as their axons leading to irreversible loss of sight. Medical management of the intraocular pressure (IOP) still represents the gold standard in glaucoma therapy, which only manages a risk factor and does not directly address the neurodegenerative component of this eye disease. Recently, our group showed that antibody derived immunopeptides (encoding complementarity-determining regions, CDRs) provide attractive glaucoma medication candidates and directly interfere its pathogenic mechanisms by different modes of action. In accordance with these findings, the present study showed the synthetic CDR2 peptide (INSDGSSTSYADSVK) significantly increased the RGCs viability in vitro in a concentration-dependent manner (p < 0.05 using a CDR2 concentration of 50 µg/mL). Employing state-of the-art immunoprecipitation experiments, we confirmed that synthetic CDR2 exhibited a high affinity towards the retinal target protein histone H3.1 (HIST1H3A) (p < 0.001 and log2 fold change > 3). Furthermore, virtual docking analyses predicted potential CDR2-specific binding regions of HIST1H3A, which might represent essential PTM sites for epigenetic regulations. Quantitative MS analysis revealed that 39 proteins were significantly changed between CDR2-treated and untreated control retinae (p < 0.05). An up-regulation of proteins involved in the energy production (e.g., ATP5F1B and MT-CO2) as well as the regulatory ubiquitin proteasome system (e.g., PSMC5) was induced by the synthetic CDR2 peptide. On the other hand, metabolic key enzymes (e.g., DDAH1 and MAOB) as well as ER stress-related proteins (e.g., SEC22B and VCP) were found with low abundancy in CDR2-treated retinae and were also partially confirmed by microarray technology. Based on these findings, it can be hypothesized that the specific protein-peptide interaction influences the regulatory epigenetic function of HIST1H3A promoting the neuroprotective mechanism on RGCs in vitro. It also might serve as basis for a synergistic immunotherapy of glaucoma in the future.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:26:49.108.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carsten Schmelter
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-25 00:56:50	ID requested
1	2022-11-09 03:12:53	announced
⏵ 2	2023-11-14 08:26:49	announced	2023-11-14: Updated project metadata.

Fomo KN, Schmelter C, Atta J, Beutgen VM, Schwarz R, Perumal N, Govind G, Speck T, Pfeiffer N, Grus FH, Synthetic antibody-derived immunopeptide provides neuroprotection in glaucoma through molecular interaction with retinal protein histone H3.1. Front Med (Lausanne), 9():993351(2022) [pubmed]

submitter keyword: Glaucoma, CDR2, Neuroprotection, HIST1H3A

Prof. Dr. Dr. FH Grus
contact affiliation	Department of Experimental and Translational Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
contact email	grus@eye-research.org
lab head
Carsten Schmelter
contact affiliation	Experimental and Translational Ophthalmology, University Medical Care Centre Mainz
contact email	carstenschmelter86@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034046
     1. Label: PRIDE project
     2. Name: Synthetic antibody-derived immunopeptide provides neuroprotection in glaucoma through molecular interaction with retinal protein Histone H3.1