5N48

Structure of Anticalin N9B in complex with extra-domain B of human oncofetal fibronectin

Summary for 5N48

• Entry DOI: 10.2210/pdb5n48/pdb
• Related: 4gh7 5n47
• Descriptor: Neutrophil gelatinase-associated lipocalin, Fibronectin (3 entities in total)
• Functional Keywords: lipocalin, anticalin, lipocalin-based binding protein, protein binding, human fibronectin, oncofetal splice variant, fn type iii domain, extra-domain b, eiiib, ed-b, extracellular matrix
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted : P80188; Secreted, extracellular space, extracellular matrix: P02751
• Total number of polymer chains: 4
• Total formula weight: 65988.48

Authors

Schiefner, A.,Skerra, A. (deposition date: 2017-02-10, release date: 2018-02-14, Last modification date: 2024-11-20)

Primary citation

Schiefner, A.,Gebauer, M.,Richter, A.,Skerra, A.
Anticalins Reveal High Plasticity in the Mode of Complex Formation with a Common Tumor Antigen.
Structure, 26:649-656.e3, 2018

PubMed Abstract: We describe the comparative X-ray structural analysis of three Anticalin proteins directed against the extra-domain B (ED-B) of oncofetal fibronectin (Fn), a validated marker of tumor neoangiogenesis. The Anticalins were engineered from the human lipocalin 2 (Lcn2) scaffold via targeted randomization of the structurally variable loop region and selection by phage display, resulting in 15-19 exchanged residues. While the four reshaped loops exhibit diverse conformations (with shifts in Cα positions up to 20.4 Å), the β-barrel core of the lipocalin remains strongly conserved, thus confirming the extraordinary robustness of this scaffold. All three Anticalins bind the cc' hairpin loop of ED-B, the most exposed motif in the context of its neighboring Fn domains, but reveal entirely different binding modes, with orientations differing by up to 180°. Hence, each Anticalin recognizes its molecular target in an individual manner, in line with the distinct epitope specificities previously seen in binding experiments.

PubMed: 29526433
DOI: 10.1016/j.str.2018.02.003

Experimental method

X-RAY DIFFRACTION (1.6 Å)