7QE3

Se-M variant of B-trefoil lectin from Salpingoeca rosetta in complex with GalNAc

This is a non-PDB format compatible entry.

Summary for 7QE3

• Entry DOI: 10.2210/pdb7qe3/pdb
• Descriptor: Sarol-1, 2-acetamido-2-deoxy-beta-D-galactopyranose, 1,2-ETHANEDIOL, ... (7 entities in total)
• Functional Keywords: lectin, galnac, b-trefoil, pore forming lectin, sugar binding protein
• Biological source: Salpingoeca rosetta
• Total number of polymer chains: 2
• Total formula weight: 79489.59

Authors

Notova, S.,Varrot, A. (deposition date: 2021-12-01, release date: 2022-09-14, Last modification date: 2024-10-16)

Primary citation

Notova, S.,Bonnardel, F.,Rosato, F.,Siukstaite, L.,Schwaiger, J.,Lim, J.H.,Bovin, N.,Varrot, A.,Ogawa, Y.,Romer, W.,Lisacek, F.,Imberty, A.
The choanoflagellate pore-forming lectin SaroL-1 punches holes in cancer cells by targeting the tumor-related glycosphingolipid Gb3.
Commun Biol, 5:954-954, 2022

PubMed Abstract: Choanoflagellates are primitive protozoa used as models for animal evolution. They express a large variety of multi-domain proteins contributing to adhesion and cell communication, thereby providing a rich repertoire of molecules for biotechnology. Adhesion often involves proteins adopting a β-trefoil fold with carbohydrate-binding properties therefore classified as lectins. Sequence database screening with a dedicated method resulted in TrefLec, a database of 44714 β-trefoil candidate lectins across 4497 species. TrefLec was searched for original domain combinations, which led to single out SaroL-1 in the choanoflagellate Salpingoeca rosetta, that contains both β-trefoil and aerolysin-like pore-forming domains. Recombinant SaroL-1 is shown to bind galactose and derivatives, with a stronger affinity for cancer-related α-galactosylated epitopes such as the glycosphingolipid Gb3, when embedded in giant unilamellar vesicles or cell membranes. Crystal structures of complexes with Gb3 trisaccharide and GalNAc provided the basis for building a model of the oligomeric pore. Finally, recognition of the αGal epitope on glycolipids required for hemolysis of rabbit erythrocytes suggests that toxicity on cancer cells is achieved through carbohydrate-dependent pore-formation.

PubMed: 36097056
DOI: 10.1038/s42003-022-03869-w

Experimental method

X-RAY DIFFRACTION (2.2 Å)