对Siglec-15的结构洞察力揭示了它通过整合素CD11bb与T细胞相互作用的糖化依赖性
Maria Pia Lenza1, Leire Egia-Mendikute2, Asier Antoñana-Vildosola2
1Chemical Glycobiology lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 800, 48160, Derio, Bizkaia, Spain.
Nature communications
|June 13, 2023
概括
酸结合性Ig样性莱克15 (Siglec-15) 是癌症免疫治疗的目标. 这项研究揭示了它的结构以及它如何与T细胞结合,突出显示了糖基化.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 酸结合性Ig-like lectin 15 (Siglec-15) 是一种免疫调节剂,也是癌症免疫疗法的有前途标.
- 对Siglec-15的结构和机制的有限知识阻碍了开发有效的候选药物.
研究的目的:
- 为了阐明Siglec-15的晶体结构及其结合表位.
- 了解Siglec-15与各种酸的结合方式及其与T细胞的相互作用.
主要方法:
- 与抗Siglec-15 阻断抗体共同结晶.
- 和转移差异核磁共振 (STD-NMR) 光谱学.
- 分子动力学模拟.分子动力学模拟.
- 对Siglec-15与T细胞结合的分析和结合伙伴的识别.
主要成果:
- 确定了Siglec-15的晶体结构及其与抗体结合的表位.
- 揭示了Siglec-15与α(2,3) 和α(2,6) 结合的酸的结合,包括与癌症相关的酸-Tn (STn) 糖形.
- 证明SIGLEC-15与T细胞的结合取决于与α(2,3) 和α(2,6) 结合的糖,并与白细胞整体蛋白CD11b相互作用.
结论:
- 本研究提供了对Siglec-15.5的全面结构理解.
- 糖化在调节Siglec-15与T细胞的相互作用和免疫反应方面发挥着至关重要的作用.
- 这些发现为开发新的Siglec-15向癌症免疫疗法铺平了道路.
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