Essentials of Glycobiology May 15th., 2008 Ajit Varki

1. Essentials of GlycobiologyMay 15th., 2008Ajit Varki Lecture 15 Chapter 28. R-type Lectins

2. Biological Roles of Glycans Soluble Glycan-Binding Proteins

4. Two Classes of GBPs - Lectins and GAG Binding Proteins

5. The R-type lectin superfamily. Different groups within the family are indicated with the domain structures shown.

6. General Questions for Lecture 15 1. Describe the differences and similarities of Ricin-I and Ricin. 2. For ricin and other ribosome inactivating toxins to kill cells, it must first gain access to the cytoplasm. How does this occur? How would you exploit this mechanism to deliver cargo to different sites in a cell? 3. Explain how a cell that becomes resistant to one type of toxic lectin could become sensitive to another? 4. What are the functions of R-type lectin domains found in enzymes such as glycosyltransferases and glycosidases? 5. Discuss an example of a receptor that contains more than one type of lectin domain. 6. Describe examples of animal lectins that engage glycan ligands in both cis and trans configurations.

7. Ricin and abrin. (a) Photographs showing the leaves and seeds of Ricinus communis and the seeds of Abrus precatorius. R. communis is commonly called the castor-oil plant and the seeds are castor beans. The A. precatorius seeds are sometimes called rosary pea, coral bead plant, or jequirity bean. (b) The crystal structure of ricin refined to 2.5 Å. Describe the differences and similarities of Ricin-I and Ricin.

8. Pathway of ricin uptake by cells and the mechanism by which the toxic activity of the A chain in the cytoplasm results in cell death. 2. For ricin and other ribosome inactivating toxins to kill cells, it must first gain access to the cytoplasm. How does this occur? How would you exploit this mechanism to deliver cargo to different sites in a cell?

9. Members of the mannose receptor family of R-type lectins. These proteins are also in the Ctype lectin family and represent a unique group of lectins with more than one type of lectin domain. 5. Discuss an example of a receptor that contains more than one type of lectin domain.

10. Structures of the β-trefoil R-type domains in different proteins. (Top) Cysteine-rich R-type domain of the mannose receptor (MR) in complex with 4-O-sulfated GalNAc; ricin B chain in complex with galactose; and acidic fibroblast growth factor (aFGF) in complex with sulfated heparan decasaccharide. (Bottom) Streptomyces lividans endo-β1 4-xylanase 10A in complex with lactose.

11. Structure and function of UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferases (ppGalNAcTs). 4. What are the functions of R-type lectin domains found in enzymes such as glycosyltransferases and glycosidases?

12. General Questions for Lecture 15 3. Explain how a cell that becomes resistant to one type of toxic lectin could become sensitive to another? 6. Describe examples of animal lectins that engage glycan ligands in both cis and trans configurations.

13. FIGURE 13.15. Structure and synthesis of N-glycans bearing terminal N-acetylgalactosamine (GalNAc), including sulfated GalNAc on pituitary hormones lutropin (LH) and thyrotropin (TSH). "LacdiNAc" "LacNAc"