9VE9

Hemoglobin amyloid fibril

Summary for 9VE9

• Entry DOI: 10.2210/pdb9ve9/pdb
• EMDB information: 64995
• Descriptor: Hemoglobin subunit beta (1 entity in total)
• Functional Keywords: protein fibril
• Biological source: Bos taurus (domestic cattle)
• Total number of polymer chains: 10
• Total formula weight: 159773.82

Authors

Li, S.,Cao, Q.,Cao, Y. (deposition date: 2025-06-09, release date: 2026-06-17, Last modification date: 2026-09-16)

Primary citation

Liu, X.,Li, S.,Wu, G.,Li, S.,Huang, L.S.,Li, X.,Zhao, Y.,Lu, W.,Sun, C.,Cao, Q.,Fang, Y.,Cao, Y.
Hemoglobin's alpha-Helix-to-beta-Sheet Transition Enables Targeted mRNA Delivery to the Lung.
Adv Sci, 13:e76092-e76092, 2026

PubMed Abstract: Effective treatment of pulmonary diseases remains constrained by the scarcity of delivery systems capable of selective tissue targeting. Herein, we report a lung-targeting platform created through the structural repurposing of hemoglobin (Hb). Acidic heating enables a conformational shift of Hb from α-helix to β-sheet, leading to its self-assembly into fibrils (HbFs). Unexpectedly, intravenously injected HbFs exhibit rapid and specific accumulation in the lungs. Cryo-electron microscopy (cryo-EM) structure determination revealed a fibril surface rich in positively charged residues, which facilitates two key functions: selective binding to circulating platelets via a hitchhiking mechanism for lung targeting, and efficient electrostatic complexation with mRNA. In a therapeutic application, HbFs loaded with mRNA encoding an interleukin-11 single-chain fragment variable (IL-11 scFv) were administered in a murine model of bleomycin-induced pulmonary fibrosis. The formulation achieved lung-specific delivery with predominant uptake by pulmonary fibroblasts, enabling sustained local IL-11 scFv expression. Consequently, treatment significantly suppressed fibroblast activation and migration, attenuated collagen deposition, restored lung function. This work establishes HbFs as a novel protein‑based vehicle for targeted mRNA delivery, leveraging natural cellular trafficking pathways to enable localized therapy for lung disorders.

PubMed: 42284495
DOI: 10.1002/advs.76092

Experimental method

ELECTRON MICROSCOPY (3.26 Å)