lecture012909 - Glycans linked to lipids lipid precursors...

Info icon This preview shows pages 1–19. Sign up to view the full content.

View Full Document Right Arrow Icon
Glycans linked to lipids, lipid precursors, and glycans in N-linkage to protein 1/29/07
Image of page 1

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Large O-linked Glycosaminoglycans and poly- lactosamine structures Glycoprotein N-linked and O- linked oligosaccharides Glycolipid oligosaccharides
Image of page 2
Glycan synthesis in a cellular context
Image of page 3

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Overview From ER through Trans-Golgi and points inbetween
Image of page 4
On and into the ER Dolichol-P-X Glycosyl phosphatidylinositol (GPI) Glycosphingolipids (GSL)
Image of page 5

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Schenk, B. et al. Glycobiology 2001 11:61R-70R; doi:10.1093/glycob/11.5.61R Topological model for the enzymatic reactions leading to Dol-P biosynthesis de novo on the cytoplasmic face of the ER
Image of page 6
Biosynthesis of N-Glycans: Production of GlcNAc-P-P-Dolichol Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79 GlcNAc Man Gal Sia Fuc Glc Dolichol Tunicamycin Blocks - not very specific!
Image of page 7

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Biosynthesis of the N-Glycan Precursor on the Cytosolic Leaflet of the Endoplasmic Reticulum (ER) Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79 GlcNAc Man Gal Sia Fuc Glc CDG = Congenital Disorder of Glycosylation in Humans
Image of page 8
Biosynthesis of the N-Glycan Precursor on Lumenal Leaflet of ER Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79 GlcNAc Man Gal Sia Fuc Glc
Image of page 9

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Completion of Biosynthesis of N-Glycan Precursor on Lumenal Leaflet of ER - and Transfer to Protein Adapted from Marquardt T, Denecke J. Eur J Pediatr. 2003 Jun;162(6):359-79 GlcNAc Man Gal Sia Fuc Glc
Image of page 10
Schenk, B. et al. Glycobiology 2001 11:61R-70R; doi:10.1093/glycob/11.5.61R Topological model for lipid intermediate synthesis, translocation and the role for Dol-P-P/Dol-P phosphatases in the recycling of Dol-P-P/Dol-P in the ER
Image of page 11

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
ER glycolipid synthesis Dolichol-P-X Glycosyl phosphatidylinositol (GPI)
Image of page 12
Examples of GPI-Anchored Proteins Cell surface hydrolases alkaline phosphatase acetylcholinesterase 5 ʼ nucleotidase Adhesion molecules neural cell adhesion molecule heparan sulfate proteoglycan Others decay accelerating factor scrapie prion protein folate receptor Protozoal antigens trypanosome VSG leishmanial protease plasmodium antigens Mammalian antigens Thy-1 carcinoembryonic antigen After Hart, G
Image of page 13

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Structure of the Basic GPI Anchor Etn P INOSITOL P = Mannose (Man) = Glucosamine Etn = Ethanolamine P = Phosphate NH 2 NH 2 Pig-A PNH Defect GPI-Linked Protein Cell Surface Membrane After Hart, G
Image of page 14
Structural Analysis of the GPI Anchor Enzymatic and chemical cleavage sites are useful in identifying GPI anchored membrane proteins After Hart, G
Image of page 15

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
After Freeze, H
Image of page 16
Biosynthesis of GPI anchors • The first step in biosynthesis of the GPI anchor requires at least four genes • One of them, PIG-A is an X-linked gene Mutation in PNH MUTATIONS IN DOL-P-MAN SYN AND USE After Freeze, H
Image of page 17

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
Paroxysmal Nocturnal Hemoglobinuria A hematopoietic stem cell disorder characterized by intravascular hemolytic anemia. Abnormal blood cells lack GPI-anchored proteins due to a mutation in the PIG-A gene.
Image of page 18
Image of page 19
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern