Recognition of Endogenous Ligands by C-Type Lectins:Interaction of Serum Mannan-binding Protein with Tumor-associated Oligosaccharide Epitopes

  • Kawasaki Nobuko
    Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan
  • Kawasaki Toshisuke
    Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan

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Other Title
  • レクチンによる内因性リガンドの認識: 血清マンナン結合タンパク質と腫瘍関連糖鎖エピトープの相互作用
  • レクチンによる内因性リガンドの認識--血清マンナン結合タンパク質と腫瘍関連糖鎖エピトープの相互作用[含 英語文]
  • レクチン ニ ヨル ナイインセイ リガンド ノ ニンシキ ケッセイ マンナン ケツゴウ タンパクシツ ト シュヨウ カンレン トウサ エピトープ ノ ソウゴ サヨウ ガン エイゴブン

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Abstract

Animal lectins have contributed greatly to under-standing of the physiological significance of glycans in man and animals. Mannan-binding protein (MBP) binds to mannose, N-acetylglucosamine and L-fucose via the carbohydrate binding sites in its carbohydrate recognition domain (CRD). In pathogenic microorganisms, manno-oligosaccharides on the cell surface appear to be the major glycans involved in the interaction with MBP, whereas in human colorectal carcinoma SW1116 cells, which are endogenous target cells of MBP, Lewis (Le)-type oligosaccharides with the type I structure appear to play a major role in the interaction with the lectin. In fact, MBP ligand oligosaccharides (MLO), which have complex type N-glycans with at least 4 Fuc(Hex-HexNAc) units, have been isolated with an MBP affinity column, whereas complex type N-glycans having 3 or less Fuc(Hex-HexNAc) units as well as high-mannose type structures (Man5 to Man8) did not bind to the MBP affinity column. The structures of MLO are very unique and distinct from those of other previously reported tumor-specific carbohydrate antigens, and thus should be considered as representative of a new family of tumor-associated carbohydrate antigens. The reasons why and how MLO exhibits such strong affinity to MBP are not clear at present but computer modeling suggested the possibility that a MBP-Lewis oligosaccharides complex may be formed between the trimeric structure of the carbohydrate recognition domain (CRD) and Leb-(Lea)x4-Lex, a typical example of the nonreducing terminal oligosaccharide structure of MLO.

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