PXD066532 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Integrative structural analysis defines how LRPAP1 modulates ligand binding in LRP2 |
| Description | The low density lipoprotein receptor-related protein 2 (LRP2 or megalin) is a multiligand endocytic receptor implicated in the homeostasis of several organs. Mutations in the LRP2 gene are associated with severe systemic disease. It is well-know that the low density lipoprotein receptor-related protein-associated protein 1 (LRPAP1 or RAP) interacts with LRP2 modulating its function. A single copy of LRPAP1 was shown to interact with complement-type repeats in LRP2, however this domain is highly redundant in LRP2, hinting at a different stoichiometry of the complex. Here, using cryogenic-electron microscopy, AlphaFold and cross-linking mass spectrometry, we provide structural insights into human recombinant LRP2 in the presence and absence of LRPAP1. Our integrative approach reveals three additional LRPAP1 sites in LRP2. Some of these LRPAP1 binding regions overlap with ligand binding sites. This finding, supported by competitive in vitro binding assays supports the hypothesis that LRPAP1 acts as a direct modulator of LRP2's ligand-binding activity. In addition, we identify several pathogenic LRP2 mutations located at the LRP2-LRPAP1 interface and LRPAP1 binding regions unique to LRP2 within the LRP family. Taken together, our study provides a broader molecular landscape of LRP2-LRPAP1 interactions, offering insights into its clinical and functional role. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-21 |
| AnnouncementXML | Submission_2026-03-21_15:31:38.776.xml |
| DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD066532 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Andrea Graziadei |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-07-24 07:16:56 | ID requested | |
| ⏵ 1 | 2026-03-21 15:31:39 | announced | |
Publication List
Keyword List
| submitter keyword: Crosslinking MS, Cross-linking MS, Megalin, LRPAP1, XL-MS, endocytosis, LRP2, RAP |
Contact List
| Andrea Graziadei |
|---|
| contact affiliation | Human Technopole, 20157, Milan, Italy |
| contact email | andrea.graziadei@fht.org |
| lab head | |
| Andrea Graziadei |
|---|
| contact affiliation | Human Technopole |
| contact email | andrea.graziadei@fht.org |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD066532
- Label: PRIDE project
- Name: Integrative structural analysis defines how LRPAP1 modulates ligand binding in LRP2
