Structural basis for the delivery of activated sialic acid into Golgi for sialyation
Structural basis for the delivery of activated sialic acid into Golgi for sialyation
复制标题
DOI：
10.1038/s41594-019-0225-y
复制
发表时间：
2019-06-01
影响因子：
16.8
通讯作者：
Drew，David
中科院分区：
文献类型：
--
作者：
Nji，Emmanuel;Gulati，Ashutosh;Drew，David
唾液酸修饰分泌性糖蛋白和糖脂对许多生理和病理过程至关重要。唾液酸化依赖于以CMP-唾液酸的形式向高尔基体细胞器中持续供应唾液酸。CMP-唾液酸转运蛋白（CST）将CMP-唾液酸转运到高尔基体中。人CST中的突变与糖基化病症相关，并且CST对于糖通路工程化是重要的，因为它对于治疗性糖蛋白的唾液酸化效率是关键的。CMP-唾液酸如何被识别并跨高尔基体膜转运以交换CMP的机制知之甚少。在这里，我们已经确定了玉米CST与CMP复合物的晶体结构。我们的结论是，特异性的CST CMP-唾液酸的核苷酸CMP的识别建立到这样的程度，他们是机械能够被动和耦合的反向转运活性。
The decoration of secretory glycoproteins and glycolipids with sialic acid is critical to many physiological and pathological processes. Sialyation is dependent on a continuous supply of sialic acid into Golgi organelles in the form of CMP-sialic acid. Translocation of CMP-sialic acid into Golgi is carried out by the CMP-sialic acid transporter (CST). Mutations in human CST are linked to glycosylation disorders, and CST is important for glycopathway engineering, as it is critical for sialyation efficiency of therapeutic glycoproteins. The mechanism of how CMP-sialic acid is recognized and translocated across Golgi membranes in exchange for CMP is poorly understood. Here we have determined the crystal structure of aZea maysCST in complex with CMP. We conclude that the specificity of CST for CMP-sialic acid is established by the recognition of the nucleotide CMP to such an extent that they are mechanistically capable of both passive and coupled antiporter activity.