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Computational design of a symmetrical β-trefoil lectin with cancer cell binding activity

Tijdschriftbijdrage - Tijdschriftartikel

Computational protein design has advanced very rapidly over the last decade, but there remain few examples of artificial proteins with direct medical applications. This study describes a new artificial β-trefoil lectin that recognises Burkitt's lymphoma cells, and which was designed with the intention of finding a basis for novel cancer treatments or diagnostics. The new protein, called "Mitsuba", is based on the structure of the natural shellfish lectin MytiLec-1, a member of a small lectin family that uses unique sequence motifs to bind α-D-galactose. The three subdomains of MytiLec-1 each carry one galactose binding site, and the 149-residue protein forms a tight dimer in solution. Mitsuba (meaning "three-leaf" in Japanese) was created by symmetry constraining the structure of a MytiLec-1 subunit, resulting in a 150-residue sequence that contains three identical tandem repeats. Mitsuba-1 was expressed and crystallised to confirm the X-ray structure matches the predicted model. Mitsuba-1 recognises cancer cells that express globotriose (Galα(1,4)Galβ(1,4)Glc) on the surface, but the cytotoxicity is abolished.
Tijdschrift: Scientific Reports
ISSN: 2045-2322
Issue: 1
Volume: 7
Jaar van publicatie:2017
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:2
CSS-citation score:1
Auteurs:International
Authors from:Higher Education