1 / 22

Lecture 6 O-GalNac Glycans C-type Lectins

Lecture 6 O-GalNac Glycans C-type Lectins. The Glycome is Rich. Man. Yeast mannoproteins a -dystroglycan. Nuclear Proteins Cytoplasmic Proteins. GalNAc. Fuc. GlcNAc. Ser/Thr. Ser/Thr. Ser/Thr. Ser/Thr. Mucins. Notch Coagulation Factors Fibrinolytic Factors. Examples of O-Glycans.

wells
Télécharger la présentation

Lecture 6 O-GalNac Glycans C-type Lectins

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lecture 6O-GalNac GlycansC-type Lectins

  2. The Glycome is Rich

  3. Man Yeast mannoproteins a-dystroglycan Nuclear Proteins Cytoplasmic Proteins GalNAc Fuc GlcNAc Ser/Thr Ser/Thr Ser/Thr Ser/Thr Mucins Notch Coagulation Factors Fibrinolytic Factors Examples of O-Glycans

  4. Glc Xyl Man Glc Gal GlcNAc Ser Ser Thr Rho proteins Worm Collagens Dictyostelium proteins Proteoglycans (Glycosaminglycans) More O-glycans

  5. Gal Glc Ara Gal GlcNAc HydroxyLys HydroxyPro Tyr Collagen C1q complement Plant glycoproteins Dictyostelium Glycogenin Even more….

  6. O H O H H O N A c H C 2 N H 2 O-Glycosidic Linkage O-glycosidic linkage is sensitive to alkali (regardless of stereochemistry) b-elimination GalNAc H O H H H a H O C C H Ser O :OH

  7. Ribbon drawing of the ppGaNTase-T1 crystal structure Fritz, Timothy A. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 15307-15312

  8. Modeled binding of a MUC1 glycopeptide to ppGaNTase-T1 Fritz, Timothy A. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 15307-15312

  9. Core 1 Core 2 Core 3 Core 4 b3 b6 Ser/Thr Core 6? Core 7 Core 8 Core 5 b6 a6 a3 b3 a3 b3 b3 b6 Ser/Thr Ser/Thr Ser/Thr Ser/Thr Ser/Thr Ser/Thr Ser/Thr Other Core O-Glycan Structures

  10. ST6GalNAc III, IV, I, II a3 b3 a6 b3 disialyl T-antigen ST3Gal-I, II, IV b3GalT b6GlcNAcT b3 b3 b6 Ser/Thr Ser/Thr Ser/Thr Tn-antigen T-antigen Core 2 ST6GalNAc-II, I ST6GalNAc-I a6 b3 a6 sialyl Tn-antigen sialyl T-antigen

  11. b3GalT Ser/Thr b3 Ser/Thr Cosmc • Tn-antigens accumulate due to loss of b3Gal transferase activity • No mutations in b3GalT; message is expressed • Missing Cosmc (Core 1 b3GalT -specific molecular chaperone, Xq23 • 25% identity, >40% homology to b3GalT • Absence of Cosmc results in proteosome degradation of b3GalT Cosmc Tn-antigen T-antigen Ju & Cummings (2002) PNAS 99:16613-8

  12. Is Cosmc a Chaperone? T-synthase + Mut Cosmc T-synthase + Wt Cosmc His-tagged Cosmc HPC4 tagged T-synthase Ni+ purification, Western with mAb to HPC4 T-synthase Total Bound to Ni+ Not bound to Ni+

  13. a3 b4 a3 b3 b4 b3 b4 a3 b3 b6 Outer Chain Assembly • Sequential action of b4GalT and b3GlcNAcT gives rise to polylactosamine chains (Type II repeats) • Type I repeats (Galb3GlcNAcb3) also occur • GlcNAcb6Gal branches (I-antigen) can occur • The ends of the chains are capped in a-linked sugars, e.g. a3/4Fuc and a3/6sialic acids • Terminal structures make up important blood group determinants, e.g. the Lewis antigens a Ser/Thr

  14. Intestinal Epithelium stained with Periodic acid-Schiff’s Reagent

  15. Mucins • 11p15 family (MUC2, MUC5AC, MUC5B, MUC6) probably responsible for the formation of mucus layers • 7q22 family (MUC3A, MUC3B, MUC12), 1q21 (MUC1), and 3q (MUC4, MUC13) are membrane mucins • Mucin families are not necessairly related to each other, convergent evolution Dekker et al. (2002) TIBS 27:126

  16. C-type Lectins

  17. Leukocyte Rolling Tim Springer, Harvard

More Related