Transcript Document

Essentials of Glycobiology
May 15th., 2008
Ajit Varki
Lecture 15
Chapter 28. R-type Lectins
Biological Roles of Glycans
Soluble
Glycan-Binding
Proteins
Two Classes of GBPs - Lectins and GAG Binding Proteins
The R-type lectin superfamily.
Different groups within the family are indicated with the domain structures shown.
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.
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.
1.
Describe the
differences and
similarities of
Ricin-I and Ricin.
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?
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.
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.
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?
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.
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"