Question

2. The tetrasaccharide below is Sialyl-Lewis. (1) Give the name of protein that binds to Sialyl-Lewis. (2) Explain a specific biological process that occurs when Sialyl-Lewis' binds to its binding protein (4 pts). Но HOY оно он HO HNA o= HO HON Fotofo LO OH Ho Tono on FoZon of HO OH

Answer 1

Answer

Selectin is the protein that binds to Sialy- Lewisx.

They have remarkably similar protein folds and carbohydrate binding residues, leading to overlap in the glycans to which they bind. Selectins bind to the sialyl Lewis X (SLexx) determinant “NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc.” However, SLexx, per se, does not constitute an effective selectin receptor.

Sialyl-Lewisx is important in leukocyte tethering and rolling. Leukocytes move through the blood stream and then tether themselves to the endothelial wall and roll along the endothelial tissue to determine if they want to leave the bloodstream to get to necessary tissue. Sialyl-Lewisx is a necessary partner for the three selectins that bind the leukocyte and endothelial cells. When sialyl-Lewisx is part of an O-glycan and attached to CD34 it can then bind to L-selectin. For the binding to L-selectin to occur sialyl-Lewisx must undergo sulfation. For sialyl-Lewisx to bind to P-selectin, an O-linked glycan near the N-terminus of P-Selectin Glycoprotein Ligand-1 (PSGL-1) is modified with sialyl-Lewisx and in combination with nearby tyrosine residues modified with sulfate, forms the binding contact for P-selectin. For sialyl-Lewisx to bind to E-selectin it can be part of either an N-linked or O-linked glycan attached to cell surface glycoproteins such as PSGL-1, CD43 or CD44. This sialyl-Lewisx mediated binding to selectins allows circulating leukocytes to stick to and roll along endothelial cells lining blood vessels thereby enabling the leukocytes to accumulate at a site of vascular inflammation.