A class of secreted mammalian peptides with potential to expand cell-cell communication.
A class of secreted mammalian peptides with potential to expand cell-cell communication.
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一类分泌的哺乳动物肽，具有扩大细胞间通讯的潜力。
DOI：
10.1101/2023.06.02.543503
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Long,JonathanZ
中科院分区：
文献类型：
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作者：
Wiggenhorn,AmandaL;Abuzaid,HindZ;Coassolo,Laetitia;Li,VeronicaL;Tanzo,JuliaT;Wei,Wei;Lyu,Xuchao;Svensson,KatrinJ;Long,JonathanZ
肽激素和神经肽是控制哺乳动物体内平衡和生理各方面的信号分子。在这里，我们提供了内源性存在一系列不同种类的血源性肽的证据，我们称之为“封顶肽”。带帽肽是分泌蛋白的片段，由两种翻译后修饰——n端热谷氨酰化和c端酰胺化——的存在来定义，它们作为中间序列的化学“帽”。封顶肽与其他信号肽具有许多共同的调节特征，包括动态生理调节。CAP-TAC1是一种速激肽神经肽样分子，是哺乳动物速激肽受体的纳米分子激动剂。第二种封顶肽CAP-GDF15是一种从全长GDF15的前肽区切割出来的12聚体肽，与规范的GDF15激素一样，也能减少食物摄入和体重。帽端肽是一类潜在的大型信号分子，在哺乳动物生理学中具有广泛调节细胞间通讯的潜力。
Peptide hormones and neuropeptides are signaling molecules that control diverse aspects of mammalian homeostasis and physiology. Here we provide evidence for the endogenous presence of a sequence diverse class of blood-borne peptides that we call “capped peptides.” Capped peptides are fragments of secreted proteins and defined by the presence of two post-translational modifications – N-terminal pyroglutamylation and C-terminal amidation – which function as chemical “caps” of the intervening sequence. Capped peptides share many regulatory characteristics in common with that of other signaling peptides, including dynamic physiologic regulation. One capped peptide, CAP-TAC1, is a tachykinin neuropeptide-like molecule and a nanomolar agonist of mammalian tachykinin receptors. A second capped peptide, CAP-GDF15, is a 12-mer peptide cleaved from the prepropeptide region of full-length GDF15 that, like the canonical GDF15 hormone, also reduces food intake and body weight. Capped peptides are a potentially large class of signaling molecules with potential to broadly regulate cell-cell communication in mammalian physiology.