D Hoffmann1, H Flörke. 1. German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing, Schloss Birlinghoven D-53754, Sankt, Augustin, Germany. daniel.hoffmann@gmd.de
Abstract
BACKGROUND: Protein glycosylation, the covalent attachment of carbohydrates, is very common, but in many cases the biological function of glycosylation is not well understood. Recently, fluorescence energy transfer experiments have shown that glycosylation can strongly change the global conformational distributions of peptides. We intend to show the physical mechanism behind this structural effect using a theoretical model. RESULTS: The framework of the hp model of Dill and coworkers is used to describe peptides and their glycosylated counterparts. Conformations are completely enumerated and exact results are obtained for the effect of glycosylation. On glycosylation, the model peptides experience conformational changes similar to those seen in experiments. This effect is highly specific for the sequence of amino acids and also depends on the size of the glycan. Experimentally testable predictions are made for related peptides. CONCLUSIONS: Glycans can, by means of entropic contributions, modulate the free energy landscape of polypeptides and thereby specifically stabilize polypeptide conformations. With respect to glycoproteins, the results suggest that the loss of chain entropy during protein folding is partly balanced by an increase in carbohydrate entropy.
BACKGROUND: Protein glycosylation, the covalent attachment of carbohydrates, is very common, but in many cases the biological function of glycosylation is not well understood. Recently, fluorescence energy transfer experiments have shown that glycosylation can strongly change the global conformational distributions of peptides. We intend to show the physical mechanism behind this structural effect using a theoretical model. RESULTS: The framework of the hp model of Dill and coworkers is used to describe peptides and their glycosylated counterparts. Conformations are completely enumerated and exact results are obtained for the effect of glycosylation. On glycosylation, the model peptides experience conformational changes similar to those seen in experiments. This effect is highly specific for the sequence of amino acids and also depends on the size of the glycan. Experimentally testable predictions are made for related peptides. CONCLUSIONS:Glycans can, by means of entropic contributions, modulate the free energy landscape of polypeptides and thereby specifically stabilize polypeptide conformations. With respect to glycoproteins, the results suggest that the loss of chain entropy during protein folding is partly balanced by an increase in carbohydrate entropy.
Authors: Mark M Chen; Alice I Bartlett; Paul S Nerenberg; Claire T Friel; Christian P R Hackenberger; Collin M Stultz; Sheena E Radford; Barbara Imperiali Journal: Proc Natl Acad Sci U S A Date: 2010-12-09 Impact factor: 11.205
Authors: Cyrielle Bonzom; Silvia Hüttner; Ekaterina Mirgorodskaya; Sun-Li Chong; Stefan Uthoff; Alexander Steinbüchel; Raymond M D Verhaert; Lisbeth Olsson Journal: AMB Express Date: 2019-08-12 Impact factor: 3.298