Univ. Grenoble Alpes, CNRS, CERMAV, 38000, Grenoble, France.
Bioorganische Chemie, Gebäude NW1, Universität Bayreuth, 95440, Bayreuth, Germany.
Angew Chem Int Ed Engl. 2018 Aug 6;57(32):10178-10181. doi: 10.1002/anie.201805165. Epub 2018 Jul 18.
The mini fungal lectin PhoSL was recombinantly produced and characterized. Despite a length of only 40 amino acids, PhoSL exclusively recognizes N-glycans with α1,6-linked fucose. Core fucosylation influences the intrinsic properties and bioactivities of mammalian N-glycoproteins and its level is linked to various cancers. Thus, PhoSL serves as a promising tool for glycoprofiling. Without structural precedence, the crystal structure was solved using the zinc anomalous signal, and revealed an interlaced trimer creating a novel protein fold termed β-prism III. Three biantennary core-fucosylated N-glycan azides of 8 to 12 sugars were cocrystallized with PhoSL. The resulting highly resolved structures gave a detailed view on how the exclusive recognition of α1,6-fucosylated N-glycans by such a small protein occurs. This work also provided a protein consensus motif for the observed specificity as well as a glimpse into N-glycan flexibility upon binding.
本文重组表达并鉴定了小型真菌凝集素 PhoSL。尽管 PhoSL 仅有 40 个氨基酸，但它却能特异性识别带有α1,6-连接岩藻糖的 N-聚糖。核心岩藻糖基化会影响哺乳动物 N-糖蛋白的固有特性和生物活性，其水平与多种癌症相关。因此，PhoSL 可以作为糖组学研究的一种有前途的工具。由于没有结构先例，本文使用锌反常信号解决了晶体结构，揭示了交错的三聚体形成了一种新型的蛋白质折叠，称为β-棱柱 III。用 PhoSL 共结晶了三个具有 8 到 12 个糖的双天线核心岩藻糖基化 N-聚糖叠氮化物。所得高分辨率结构详细说明了如此小的蛋白质如何特异性识别α1,6-岩藻糖基化的 N-聚糖。这项工作还为观察到的特异性提供了一个蛋白质共识基序，并揭示了 N-聚糖在结合时的灵活性。
