9DKZ

In situ microED structure of the Eosinophil major basic protein-1

Summary for 9DKZ

• Entry DOI: 10.2210/pdb9dkz/pdb
• Descriptor: Bone marrow proteoglycan (2 entities in total)
• Functional Keywords: effector, nanocrystal, in-situ, intracellular, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 13694.77

Authors

Yang, J.E.,Bingman, C.A.,Mitchell, J.,Mosher, D.,Wright, E.R. (deposition date: 2024-09-10, release date: 2024-09-25, Last modification date: 2024-11-13)

Primary citation

Yang, J.E.,Mitchell, J.M.,Bingman, C.A.,Mosher, D.F.,Wright, E.R.
In situ crystalline structure of the human eosinophil major basic protein-1.
Biorxiv, 2024

PubMed Abstract: Eosinophils are white blood cells that participate in innate immune responses and have an essential role in the pathogenesis of inflammatory and neoplastic disorders. Upon activation, eosinophils release cytotoxic proteins such as major basic protein-1 (MBP-1) from cytoplasmic secretory granules (SGr) wherein MBP-1 is stored as nanocrystals. How the MBP-1 nanocrystalline core is formed, stabilized, and subsequently mobilized remains unknown. Here, we report the structure of crystalline MBP-1 within SGrs of human eosinophils. The structure reveals a mechanism for intragranular crystal packing and stabilization of MBP-1 via a structurally conserved loop region that is associated with calcium-dependent carbohydrate binding in other C-type lectin (CTL) proteins. Single-cell and single-SGr profiling correlating real-space three-dimensional information from cellular montage cryo-electron tomography (cryo-ET) and microcrystal electron diffraction (MicroED) data obtained from non-activated and IL33-activated eosinophils revealed activation-dependent crystal expansion and extrusion of expanded crystals from SGr. These results suggest that MBP-1 crystals play a dynamic role in the release of SGr contents. Collectively, this research demonstrates the importance of macromolecular structure determination.

PubMed: 39416224
DOI: 10.1101/2024.10.09.617336

Experimental method

ELECTRON CRYSTALLOGRAPHY (3.2 Å)