Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Nat Struct Mol Biol. 2019 Jun;26(6):415-423. doi: 10.1038/s41594-019-0225-y. Epub 2019 May 27.
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 a Zea mays CST 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.
唾液酸对糖蛋白和糖脂的修饰对于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不断供应唾液酸。CMP-唾液酸向高尔基体的易位是由 CMP-唾液酸转运蛋白（CST）完成的。人类 CST 的突变与糖基化障碍有关，CST 对于糖途径工程很重要，因为它对于治疗性糖蛋白的唾液酸化效率至关重要。CMP-唾液酸如何被识别并穿过高尔基体膜以交换 CMP 的机制尚未完全理解。在这里，我们已经确定了与 CMP 结合的 Zea mays CST 的晶体结构。我们得出的结论是，CST 对 CMP-唾液酸的特异性是通过识别核苷酸 CMP 来建立的，以至于它们在机制上能够同时具有被动和偶联反向转运蛋白的活性。
