膜靶向增强了哺乳动物细胞中 NOD2 和 Arf6-GTPase 对 muramyl dipeptide 的结合。
Membrane targeting enhances muramyl dipeptide binding to NOD2 and Arf6-GTPase in mammalian cells.
机构信息
Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
Department of Immunology and Microbiology and Department of Chemistry, Scripps Research, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
出版信息
Chem Commun (Camb). 2022 Jun 8;58(46):6598-6601. doi: 10.1039/d2cc01903e.
To further understand the mechanisms of muramyl dipeptide (MDP) sensing by NOD2, we evaluated key properties involved in the formation of the Arf6-MDP-NOD2 complex in mammalian cells. We found that the conserved Arf aromatic triad is crucial for binding to MDP-NOD2. Mutation of Arf6 N-myristoylation and NOD2 S-palmitoylation also abrogated the formation of the Arf6-MDP-NOD2 complex. Notably, lipid-modified MDP (L18-MDP) increased Arf6-NOD2 assembly. Our results indicate recruitment of Arf6 may explain enhanced activity of lipidated MDP analogues and membrane targeting may be important in developing next-generation NOD2 agonists.
为了进一步了解 NOD2 识别二肽基肽（MDP）的机制，我们评估了在哺乳动物细胞中形成 Arf6-MDP-NOD2 复合物所涉及的关键性质。我们发现，保守的 Arf 芳香三肽对于与 MDP-NOD2 的结合至关重要。Arf6 的 N-豆蔻酰化和 NOD2 的 S-棕榈酰化突变也会破坏 Arf6-MDP-NOD2 复合物的形成。值得注意的是，脂质修饰的 MDP（L18-MDP）增加了 Arf6-NOD2 的组装。我们的研究结果表明，Arf6 的募集可能解释了脂质化 MDP 类似物活性增强的原因，而膜靶向可能是开发新一代 NOD2 激动剂的关键。
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