Dataset Information

LC-MS/MS analysis of Gd-IgA1 and secretary TfR1 cross-linked complex

ABSTRACT: The retention of galactose-deficient IgA1 (Gd-IgA1) in the glomerular mesangium is a hallmark of IgA nephropathy (IgAN). The immune complex formed by Gd-IgA1 binds to transferrin receptor 1 (TfR1) and deposits on mesangial cell, inducing cell proliferation, inflammatory response, matrix secretion, etc., causes organic damage and dysfunction of the kidney. Even though, the mechanism of how Gd-IgA1 recognize and bind to TfR1 is unclear. In this experiment, we ami to determine the specific interaction region responsible for Gd-IgA1 and TfR1. We prepared a complex of Gd-IgA1 and TfR1 by incubating the two proteins under acidic conditions and stabilizing it using the chemical cross-linking agent glutaraldehyde. And then, the gel bands corresponding to the Gd-IgA1-TfR1 complex was exexcised from the SDS-PAGE gel and analyzed by high-resolution mass spectrometry. This analysis identified fragments containing the hinge peptide sequence, with the R276 residue interacting with the E350 and D356 residues in the apical domain of TfR1. Our results reveal that the hinge peptide of Gd-IgA1 interacts specifically with the apical domain of TfR1.

INSTRUMENT(S): LTQ Orbitrap, Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Iga Glomerulonephritis

SUBMITTER: Jingpeng Fu

LAB HEAD: Xueqing Yu

PROVIDER: PXD063709 | Pride | 2025-07-14

REPOSITORIES: Pride

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Publications

Lysosome-mediated aggregation of galactose-deficient IgA1 with transferrin receptor 1 links to IgA nephropathy.

Si Meijun M Fu Jingpeng J Fang Mengting M Lu Yunfei Y Huang Junxuan J Li Haojie H Wang Peiyi P Liao Maofu M Zhu Jian J Li Peiyao P Zhong Wenzhao W Guo Zhifei Z Yang Wei W Ye Zhiming Z Hu Hongli H Yu Xueqing X

Nature communications 20250701 1

The retention of galactose-deficient IgA1 (Gd-IgA1) in the mesangium is central to IgA nephropathy (IgAN), but its intracellular fate remains unclear. Here, we show that transferrin receptor 1 (TfR1) mediates Gd-IgA1 uptake into mesangial cell lysosomes, where it forms non-digestible aggregates, disrupts lysosomal function, and triggers inflammatory responses. In renal biopsies from IgAN patients, IgA1 aggregates co-localize with TfR1 within lysosomes. In male mice, TfR1 overexpression enhanced ...[more]

PMID: 40593574

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			Action	DRS
	20230051_WRS.raw	Raw
	IgA1.csv	Csv
	checksum.txt	Txt
	sTfR1.csv	Csv