9DKZ

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

9DKZ の概要

• エントリーDOI: 10.2210/pdb9dkz/pdb
• 分子名称: Bone marrow proteoglycan (2 entities in total)
• 機能のキーワード: effector, nanocrystal, in-situ, intracellular, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13694.77

構造登録者

Yang, J.E.,Bingman, C.A.,Mitchell, J.,Mosher, D.,Wright, E.R. (登録日: 2024-09-10, 公開日: 2024-09-25, 最終更新日: 2024-11-13)

主引用文献

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

実験手法

ELECTRON CRYSTALLOGRAPHY (3.2 Å)