Abbas Massilia, Maalej Meriem, Nieto-Fabregat Ferran, Thépaut Michel, Kleman Jean-Philippe, Ayala Isabel, Molinaro Antonio, Simorre Jean-Pierre, Marchetti Roberta, Fieschi Franck, Laguri Cedric
Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble 38000, France.
Department of Chemical Sciences, University of Naples Federico II, Naples 80126, Italy.
PNAS Nexus. 2023 Sep 20;2(9):pgad310. doi: 10.1093/pnasnexus/pgad310. eCollection 2023 Sep.
Lipopolysaccharides are a hallmark of gram-negative bacteria, and their presence at the cell surface is key for bacterial integrity. As surface-exposed components, they are recognized by immunity C-type lectin receptors present on antigen-presenting cells. Human macrophage galactose lectin binds surface that presents a specific glycan motif. Nevertheless, this high-affinity interaction occurs regardless of the integrity of its canonical calcium-dependent glycan-binding site. NMR of macrophage galactose-type lectin (MGL) carbohydrate recognition domain and complete extracellular domain revealed a glycan-binding site opposite to the canonical site. A model of trimeric macrophage galactose lectin was determined based on a combination of small-angle X-ray scattering and AlphaFold. A disulfide bond positions the carbohydrate recognition domain perpendicular to the coiled-coil domain. This unique configuration for a C-type lectin orients the six glycan sites of MGL in an ideal position to bind lipopolysaccharides at the bacterial surface with high avidity.
脂多糖是革兰氏阴性菌的一个标志，它们在细胞表面的存在对于细菌的完整性至关重要。作为表面暴露成分，它们可被抗原呈递细胞上存在的免疫C型凝集素受体识别。人巨噬细胞半乳糖凝集素结合呈现特定聚糖基序的表面。然而，这种高亲和力相互作用的发生与它经典的钙依赖性聚糖结合位点的完整性无关。巨噬细胞半乳糖型凝集素（MGL）碳水化合物识别结构域和完整细胞外结构域的核磁共振显示了一个与经典位点相对的聚糖结合位点。基于小角X射线散射和AlphaFold的组合确定了三聚体巨噬细胞半乳糖凝集素的模型。一个二硫键将碳水化合物识别结构域定位成垂直于卷曲螺旋结构域。这种C型凝集素的独特构象将MGL的六个聚糖位点定位在理想位置，以便以高亲和力结合细菌表面的脂多糖。
