Glycosylation May Reduce Protein Thermodynamic Stability by Inducing a Conformational Distortion
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- 作者：Yulian Gavrilov ; Dalit Shental-Bechor ; Harry M. Greenblatt ; Yaakov Levy
- 刊名：The Journal of Physical Chemistry Letters
- 出版年：2015
- 出版时间：September 17, 2015
- 年：2015
- 卷：6
- 期：18
- 页码：3572-3577
- 全文大小：338K
- ISSN：1948-7185
文摘
Glycosylation plays not only a functional role but can also modify the biophysical properties of the modified protein. Usually, natural glycosylation results in protein stabilization; however, in vitro and in silico studies showed that sometimes glycosylation results in thermodynamic destabilization. Here, we applied coarse-grained and all-atom molecular dynamics simulations to understand the mechanism underlying the loss of stability of the MM1 protein by glycosylation. We show that the origin of the destabilization is a conformational distortion of the protein caused by the interaction of the monosaccharide with the protein surface. Though glycosylation creates new short-range glycan鈥損rotein interactions that stabilize the conjugated protein, it breaks long-range protein鈥損rotein interactions. This has a destabilizing effect because the probability of long- and short-range interactions forming differs between the folded and unfolded states. The destabilization originates not from simple loss of interactions but due to a trade-off between the short- and long-range interactions.