9-O-ACETYLATED SIALIC ACIDS HAVE WIDESPREAD BUT SELECTIVE EXPRESSION - ANALYSIS USING A CHIMERIC DUAL-FUNCTION PROBE DERIVED FROM INFLUENZA-C HEMAGGLUTININ-ESTERASE
9-O-ACETYLATED SIALIC ACIDS HAVE WIDESPREAD BUT SELECTIVE EXPRESSION - ANALYSIS USING A CHIMERIC DUAL-FUNCTION PROBE DERIVED FROM INFLUENZA-C HEMAGGLUTININ-ESTERASE
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DOI：
10.1073/pnas.91.16.7782
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发表时间：
1994-08-02
影响因子：
11.1
通讯作者：
VARKI, A
中科院分区：
文献类型：
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作者：
KLEIN, A;KRISHNA, M;VARKI, A
虽然在一些哺乳动物组织中已经报道了唾液酸的9- o乙酰化，但这种修饰在特定细胞类型和分子上的分布在很大程度上是未知的。丙型流感病毒血凝素酯酶是一种膜结合糖蛋白，它特异性地与9-O乙酰化唾液酸结合（血凝素活性），然后水解o -乙酰基（受体破坏活性）。C型流感病毒血凝素酯酶的重组可溶性形式，其中C端跨膜和细胞质结构域被人IgG的Fc部分所取代，同时保留其识别和酶功能。后一种活性可以选择性地去除结合或游离唾液酸中的9- o -乙酰基，在特定条件下也可以去除7- o -乙酰基。酯酶的不可逆失活揭示了稳定的识别活性，使分子特异性地结合9- o -乙酰化唾液酸。这些探针在某些细胞类型的大鼠组织中广泛但选择性地表达9- o -乙酰化唾液酸。极化或梯度表达的模式进一步证明了这种修饰的调节性质。直接探针的斑点和薄层板显示选择性表达9- o -乙酰化在某些糖蛋白和糖脂在这些组织。因此，9- o -乙酰化比以前认为的更广泛，发生在特定的分子和细胞类型上。
While 9-O-acetylation of sialic acids has been reported in some mammalian tissues, the distribution of this modification on specific cell types and molecules is largely unknown. The influenza C virus hemagglutinin-esterase is a membrane-bound glycoprotein that binds specifically to 9-O acetylated sialic acids (hemagglutinin activity) and then hydrolyzes the O-acetyl group (receptor-destroying activity). A recombinant soluble form of influenza C virus hemagglutinin-esterase wherein the C-terminal transmembrane and cytoplasmic domains are replaced by the Fc portion of human IgG retains both its recognition and enzymatic functions. The latter activity can selectively remove 9-O-acetyl groups from bound or free sialic acids and, under specific conditions, 7-O-acetyl groups as well. Irreversible inactivation of the esterase unmasks stable recognition activity, giving a molecule that binds specifically to 9-O-acetylated sialic acids. These probes demonstrate widespread but selective expression of 9-O-acetylated sialic acids in certain cell types of rat tissues. Patterns of polarized or gradient expression further demonstrate the regulated nature of this modification. Direct probing of blots and thin-layer plates shows selective expression of 9-O-acetylation on certain glycoproteins and glycolipids in such tissues. Thus, 9-O-acetylation is more widespread than previously thought and occurs on specific molecules and cell types.