Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
Structural Characterization of N-Linked Glycans in the Receptor Binding Domain of the SARS-CoV-2 Spike Protein and their Interactions with Human Lectins.
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DOI：
10.1002/anie.202011015
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发表时间：
2020-12-21
期刊：
影响因子：
--
通讯作者：
Ereño-Orbea J
中科院分区：
文献类型：
--
作者：
Lenza MP;Oyenarte I;Diercks T;Quintana JI;Gimeno A;Coelho H;Diniz A;Peccati F;Delgado S;Bosch A;Valle M;Millet O;Abrescia NGA;Palazón A;Marcelo F;Jiménez-Osés G;Jiménez-Barbero J;Ardá A;Ereño-Orbea J
使用 NMR 研究了人 HEK293F 细胞中表达的 SARS-CoV2 刺突糖蛋白的受体结合域的聚糖结构。不同的可能相互作用的表位已被深入分析和表征，提供了以前基于质谱的分析中未发现的聚糖结构存在的证据。 RBD 13C 标记聚糖与不同人类凝集素的相互作用也已通过 NMR 进行了评估，这些凝集素在感染过程中可能受到影响的不同器官和组织中表达。特别是，使用了15N标记的半乳糖凝集素（半乳糖凝集素-3、-7和-8 N端）、Siglecs（Siglec-8、Siglec-10）和C型凝集素（DC-SIGN、MGL）。从糖蛋白的角度或从凝集素的角度进行的补充实验已经能够解开每种情况下特定的相互作用表位。基于这些发现，提出了相互作用复合物的 3D 模型。核磁共振波谱揭示了 SARS-CoV-2 刺突糖蛋白 RBD 聚糖前所未有的结构细节。检测到了意想不到的和以前未报道过的糖表位。 RBD 糖蛋白与多种人类凝集素的相互作用已通过利用 13C-聚糖的 NMR 特征进行了仔细检查。我们的分析允许识别负责与每种凝集素相互作用的相应聚糖表位。
The glycan structures of the receptor binding domain of the SARS‐CoV2 spike glycoprotein expressed in human HEK293F cells have been studied by using NMR. The different possible interacting epitopes have been deeply analysed and characterized, providing evidence of the presence of glycan structures not found in previous MS‐based analyses. The interaction of the RBD 13C‐labelled glycans with different human lectins, which are expressed in different organs and tissues that may be affected during the infection process, has also been evaluated by NMR. In particular, 15N‐labelled galectins (galectins‐3, ‐7 and ‐8 N‐terminal), Siglecs (Siglec‐8, Siglec‐10), and C‐type lectins (DC‐SIGN, MGL) have been employed. Complementary experiments from the glycoprotein perspective or from the lectin's point of view have permitted to disentangle the specific interacting epitopes in each case. Based on these findings, 3D models of the interacting complexes have been proposed. Unprecedent structural details of the glycans of the RBD of SARS‐CoV‐2 spike glycoprotein have been revealed by NMR spectroscopy. Unexpected and non‐previously reported glycoepitopes have been detected. The interaction of the RBD glycoprotein with diverse human lectins has been scrutinised by exploiting the NMR signature of the 13C‐glycans. Our analysis permitted to identify the corresponding glycan epitopes responsible for the interaction with each lectin.
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