8UBS

Crystal structure of NrdJ-1 split intein fusion

Summary for 8UBS

• Entry DOI: 10.2210/pdb8ubs/pdb
• Descriptor: NrdJ-1, FORMIC ACID, SODIUM ION, ... (4 entities in total)
• Functional Keywords: fusion of the split intein nrdj-1., splicing
• Biological source: marine metagenome
• Total number of polymer chains: 4
• Total formula weight: 68215.87

Authors

Kofoed, C.,Ye, X.,Jeffrey, P.D.,Muir, T.W. (deposition date: 2023-09-24, release date: 2024-10-09, Last modification date: 2025-10-01)

Primary citation

Kofoed, C.,Erkalo, G.,Tay, N.E.S.,Ye, X.,Lin, Y.,Muir, T.W.
Programmable protein ligation on cell surfaces.
Nature, 645:793-800, 2025

PubMed Abstract: The surface landscapes of cells differ as a function of cell type and are frequently altered in disease contexts. Exploiting such differences is key to many therapeutic strategies and is the basis for developing diagnostic and basic-science tools. State-of-the-art strategies typically target single surface antigens, but each individual receptor rarely defines the specific cell type. The development of programmable molecular systems that integrate multiple cell-surface features to convert on-target inputs to user-defined outputs is therefore highly desirable. Here we describe an autonomous decision-making device driven by proximity-gated protein trans-splicing that allows local generation of an active protein from two otherwise inactive polypeptide fragments. We show that this protein-actuator platform can perform convergent protein ligation on designated cell surfaces, allowing highly selective generation of active proteins, which can either remain physically associated with the cell surface on which they were manufactured or be released into the surrounding milieu. Because of its intrinsic modularity and tunability, we demonstrate that the technology is compatible with different types of input, targeting modality and functional output, allowing for the localized interrogation or manipulation of cellular systems.

PubMed: 40739351
DOI: 10.1038/s41586-025-09287-2

Experimental method

X-RAY DIFFRACTION (1.95 Å)