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Myelin basic protein fragmentation by engineered human proteasomes with different catalytic phenotypes revealed direct peptide ligands of MS-associated and protective HLA class I molecules

ABSTRACT: Proteasomes exist in mammalian cells in multiple combinatorial variants due to the broadly diversified regulatory particles and catalytic subunits exchange. Here, using biotin carboxyl carrier domain of transcarboxylase from Propionibacterium shermanii fused with different proteasome subunits of catalytic and regulatory particles, we report comprehensive characterization of highly homogenous one-step purified human constitutive and immune 20S and 26S/30S proteasomes. Hydrolysis of multiple sclerosis (MS) autoantigen, myelin basic protein (MBP), by engineered human proteasomes with different catalytic phenotypes revealed peptides, which may be directly loaded on the HLA class I. Prediction of affinity of HLA class I to these peptides demonstrated that protective HLA I alleles are high affinity binders, whereas MS-associated alleles tend to have moderate-to-low affinity. Core peptide QDENPVVHFF, originated from the encephalitogenic MBP part, and its deaminated form was shown to be high affinity ligand for the protective HLA A*44, -B*40 and -B*35 alleles, demonstrating complexity of the autoimmune neurodegeneration.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Rustam Ziganshin

LAB HEAD: Alexey Belogurov

PROVIDER: PXD038387 | Pride | 2023-01-13

REPOSITORIES: Pride

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			Action	DRS
	Belogurov_082_20220930_ZR_AB_4-20.mgf	Mgf
	Belogurov_082_20220930_ZR_AB_4-20.mzid.gz	Mzid
	Belogurov_082_20220930_ZR_AB_4-20.raw	Raw
	Belogurov_084_20220930_ZR_AB_4_plus_20.mgf	Mgf
	Belogurov_084_20220930_ZR_AB_4_plus_20.mzid.gz	Mzid

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