| Aspect | Key points | Evidence |
|---|---|---|
| Verified identity | Human **PRG2** corresponds to **proteoglycan 2 / eosinophil granule major basic protein-1 (MBP-1)**; literature also refers to the precursor as **proMBP-1** and **bone marrow proteoglycan-2**. Marongiu 2023 explicitly identifies PRG2 as eosinophil granule major basic protein (MBP-1). | (pqac-00000000, pqac-00000002) |
| Precursor processing | PRG2 is produced as a **222-residue precursor (proMBP-1)** that matures by **cleavage of an acidic N-terminal propiece**, yielding the **117-residue mature MBP-1**, which is highly cationic (**pI ~11.4; net charge about +15 at pH 7**). The propiece hinders intermolecular interactions needed for crystal packing. | (pqac-00000000, pqac-00000003, pqac-00000005) |
| Domain architecture / fold | Mature MBP-1 adopts an **unusual C-type lectin-like (CTL) fold**. The in situ structure contains **2 main α-helices, 7 β-strands, 6 loops**, and **2 disulfide bonds (Cys125-Cys220 and Cys197-Cys212)**. | (pqac-00000000, pqac-00000001) |
| Carbohydrate-binding region | MBP-1 retains a **CTL-like carbohydrate-binding region**, but the in situ granule form lacks the canonical acidic residues for **Ca2+-dependent carbohydrate binding**, explaining loss of canonical lectin behavior. By contrast, purified/recrystallized MBP-1 can bind **sulfated sugars such as heparin**. | (pqac-00000003, pqac-00000004, pqac-00000006) |
| Key structural determinants | A distinctive **L4/L3 loop pocket** stabilizes **cis-Pro190** through **proline-aromatic interactions** involving residues such as **Trp185** and **Trp191**; these features contribute to **crystal packing**. Local conformational differences distinguish the in situ granule form from prior in vitro crystal structures. | (pqac-00000001, pqac-00000003, pqac-00000004, pqac-00000005) |
| Subcellular localization | MBP-1 is localized to **eosinophil secretory granules (SGr)**, where it forms the **electron-dense crystalline core** of the granule. Expression data cited in Marongiu 2023 place PRG2 in **granulocytes/eosinophils**. | (pqac-00000000, pqac-00000002, pqac-00000004) |
| Storage form | In resting eosinophils, MBP-1 is stored as **dense nanocrystals**; activated cells can show **membrane-less/free crystalline cores**. The crystal occupies a large fraction of the granule volume, increasing from **0.62 ± 0.12** in non-activated granules to **0.75 ± 0.13** in activated granules. | (pqac-00000000, pqac-00000004, pqac-00000006, pqac-00000008) |
| Functional rationale for crystallization | **Soluble MBP-1 is cytotoxic and membrane-disruptive**, whereas **proMBP-1** and the **isolated nanocrystalline cores** are reported as **nontoxic**. This supports the idea that intracellular crystallization protects eosinophils from the protein's non-selective toxicity until release. | (pqac-00000000, pqac-00000003) |
| Release / degranulation mechanism | IL33 activation is associated with **directional lattice expansion**, **nanocrystal disassembly**, and **extrusion/release** of MBP-1 crystals during eosinophil degranulation, including **piecemeal degranulation** and **compound exocytosis**. Free crystals in activated cells diffract to about **3 Å**. | (pqac-00000004, pqac-00000006, pqac-00000008) |
| Additional molecular interactions | **proMBP-1** can form a complex with **PAPP-A** through interactions involving **proline-rich motifs** in PAPP-A; this is structurally distinct from the granule crystal-packing interactions of mature MBP-1. | (pqac-00000003, pqac-00000005) |
| 2024 structural advance | Yang 2024 reported the **first in situ structure of crystalline human gMBP-1 within secretory granules**, using **cryo-ET, cryo-FIB, and MicroED**. The granule structure was solved at about **3.2 Å merged-map resolution** and deposited as **PDB 9DKZ**. | (pqac-00000001, pqac-00000006, pqac-00000009, pqac-00000010) |
| 2023 human genetics advance | Marongiu 2023 identified a Sardinian **PRG2 p.Ser148Pro** variant associated with altered **eosinophil morphology/reduced granularity** and reported that **homozygotes for rs769591668-C** had **absent or very low eosinophil counts**. Modeling suggested altered atomic fluctuations, disrupted Tyr109 contact, and increased Asp176 solvent exposure. | (pqac-00000002, pqac-00000007) |
| Overall current understanding | PRG2 encodes a **granule-packaged eosinophil effector protein** whose biology depends on **precursor neutralization**, **crystalline intragranular storage**, and **activation-triggered crystal remodeling/release**. Recent structural and human-variant studies link its **molecular architecture** directly to **granule packing, eosinophil morphology, and degranulation behavior**. | (pqac-00000000, pqac-00000002, pqac-00000004, pqac-00000010) |


*Table: This table compiles the key verified facts for human PRG2/MBP-1 from the provided 2023-2024 evidence only. It is useful as a compact reference for identity, structure, localization, mechanism, and recent developments directly tied to the cited sources.*