8PF0
Diubiquitin-derived artificial binding protein (Affilin) variant Af1 specific to oncofetal fibronectin
Summary for 8PF0
| Entry DOI | 10.2210/pdb8pf0/pdb |
| Descriptor | Affilin variant Af1 (77405), COPPER (II) ION, IMIDAZOLE, ... (4 entities in total) |
| Functional Keywords | extra domain b, edb, oncofetal fibronectin, ubiquitin, diubiqutin, affilin, beta strand register shift, strand slippage, scaffold, artificial binding protein, plasticity, directed evolution, de novo protein |
| Biological source | Homo sapiens |
| Total number of polymer chains | 1 |
| Total formula weight | 17921.46 |
| Authors | Parthier, C.,Katzschmann, A.,Fiedler, E.,Haupts, U.,Reimann, A. (deposition date: 2023-06-15, release date: 2024-06-26, Last modification date: 2024-08-14) |
| Primary citation | Katzschmann, A.,Haupts, U.,Reimann, A.,Settele, F.,Gloser-Braunig, M.,Fiedler, E.,Parthier, C. Ubiquitin-derived artificial binding proteins targeting oncofetal fibronectin reveal scaffold plasticity by beta-strand slippage. Commun Biol, 7:907-907, 2024 Cited by PubMed Abstract: Affilin proteins, artificial binding proteins based on the ubiquitin scaffold, have been generated by directed protein evolution to yield de-novo variants that bind the extra-domain B (EDB) of oncofetal fibronectin, an established marker of tumor neovasculature. The crystal structures of two EDB-specific Affilin variants reveal a striking structural plasticity of the ubiquitin scaffold, characterised by β-strand slippage, leading to different negative register shifts of the β5 strands. This process recruits amino acid residues from β5 towards the N-terminus to an adjacent loop region and subsequent residues into β5, respectively, remodeling the binding interface and leading to target specificity and affinity. Protein backbone alterations resulting from β-strand register shifts, as seen in the ubiquitin fold, can pose additional challenges to protein engineering as structural evidence of these events is still limited and they are difficult to predict. However, they can surface under the selection pressure of directed evolution and suggest that backbone plasticity allowing β-strand slippages can increase structural diversity, enhancing the evolutionary potential of a protein scaffold. PubMed: 39068227DOI: 10.1038/s42003-024-06569-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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