7QE4 の概要
エントリーDOI | 10.2210/pdb7qe4/pdb |
分子名称 | Sarol-1, 2-acetamido-2-deoxy-alpha-D-galactopyranose, 2-acetamido-2-deoxy-beta-D-galactopyranose, ... (6 entities in total) |
機能のキーワード | lectin, galnac, b-trefoil, pore forming lectin, sugar binding protein |
由来する生物種 | Salpingoeca rosetta |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 79711.73 |
構造登録者 | |
主引用文献 | 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 Cited by 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: 36097056DOI: 10.1038/s42003-022-03869-w 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.7 Å) |
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