Rosenlöcher Julia, Sandig Grit, Kannicht Christoph, Blanchard Véronique, Reinke Stefan O, Hinderlich Stephan
Laboratory of Biochemistry, Department of Life Sciences and Technology, Beuth University of Applied Sciences Berlin, Seestrasse 64, 13347 Berlin, Germany; Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
Laboratory of Biochemistry, Department of Life Sciences and Technology, Beuth University of Applied Sciences Berlin, Seestrasse 64, 13347 Berlin, Germany.
J Proteomics. 2016 Feb 16;134:85-92. doi: 10.1016/j.jprot.2015.08.011. Epub 2015 Aug 24.
Glycosylation is the most complex post-translational modification. Thus, it contributes to versatile chemical compositions of proteins, leading to high amounts of protein species. The structural heterogeneity of glycoproteins was also described by the definition of glycoforms. We therefore introduced a new term called "glycoprotein species" to join the two concepts from different fields of biology. In this study, we further determined the theoretical numbers of glycoprotein species of two recombinant glycoproteins - a therapeutical antibody and the human protease inhibitor alpha-1-antitrypsin (A1AT) - based on structural analysis of their N-glycans. Moreover, we showed that variations in the used cell lines and their cultivation conditions strongly influence the number of glycoprotein species in case of recombinant A1AT production.
Protein glycosylation is a major source for the huge amount of protein species. This study extends the sight of protein species by the following contributions: 1) The new term "glycoprotein species" was defined to introduce the concept of glycoforms into the field. 2) An estimation of the number of potential glycoprotein species of two particular glycoproteins was given. 3) The influence of production conditions for recombinant glycoproteins on glycoprotein species generation was displayed.
糖基化是最复杂的翻译后修饰。因此，它促成了蛋白质多样的化学组成，导致了大量的蛋白质种类。糖型的定义也描述了糖蛋白的结构异质性。因此，我们引入了一个新术语“糖蛋白种类”，以将来自生物学不同领域的两个概念结合起来。在本研究中，我们基于对两种重组糖蛋白——一种治疗性抗体和人蛋白酶抑制剂α-1-抗胰蛋白酶（A1AT）——的N-聚糖的结构分析，进一步确定了它们糖蛋白种类的理论数量。此外，我们表明，在重组A1AT生产过程中，所用细胞系及其培养条件的变化强烈影响糖蛋白种类的数量。
蛋白质糖基化是大量蛋白质种类的主要来源。本研究通过以下贡献扩展了对蛋白质种类的认识：1）定义了新术语“糖蛋白种类”，将糖型概念引入该领域。2）给出了两种特定糖蛋白潜在糖蛋白种类数量的估计。3）展示了重组糖蛋白生产条件对糖蛋白种类产生的影响。
