Sugar side-chains attached to proteins have a strong folding and stabilizing effect
Originally published online: April 2009
In living organisms, the correct function and activity of proteins requires their proper structure to be maintained. The saccharide side-chain of a protein, known as a glycan, is thought to be important in maintaining protein structure, activity and folding, but little is known about its role.
Now, a team led by Evan Powers and Jeffery Kelly at the Scripps Research Institute, USA, and Chi-Huey Wong at the Academia Sinica, Taiwan, has analyzed a well- defined and highly conserved saccharide core within a particular glycan1. They found that in a protein from a human immune cell receptor, the core is responsible for increasing the rate of folding and affects its stability.
The glycan studied contains three monosaccharide units that form a core. When all of the units are present, the researchers observed that the rate of glycan folding increases 4-fold and the structure is stabilized significantly – by 3.1 kcal/mol – compared to a protein with no core attached. Interestingly, when just one unit present, the protein folds just as fast and is stabilized with two-thirds of the energy. The remaining two units account for the remaining stabilization energy.
This result shows the importance of conserved saccharide cores and sheds light on potential general mechanisms for protein folding. The group is now studying similar systems to understand this relationship further.
Hanson, S.R., Culyba, E.K., Hsu, T.-L., Wong, C.-H., Kelly, J.W. & Powers, E.T. The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability. Proc. Nat. Acad. Sci. U.S.A. 2009, 106, 3131–3136