Williams BCH 444 2014 Lectures 3-6

Or polytopic type i transmembrane tm segments

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Unformatted text preview: ne proteins - establishing membrane topology Type II Type III or polytopic Type I Transmembrane (TM) segments typically consist of 20 25 hydrophobic amino acids that can assume various orientations. These segments are usually α-helical since an extended polypeptide conformation is disfavoured in a hydrophobic lipid bilayer. (equivalent to extracellular space) e.g., translocon components, Golgi proteins e.g., Receptor Tyrosine Kinases e.g., transporters (CFTR) ion channels, G protein coupled receptors In aqueous media, extended polypeptides form hydrogen bonds between their peptide bonds and surrounding water. This is not possible in a lipid bilayer. In an α-helical arrangement the amide hydrogen and carbonyl oxygen are maximally hydrogen bonded along the length of the helix. cleavable signal Hydrophobic transmembrane sequences that control membrane protein topology: stop transfer 20-30 hydrophobic aa signal anchor signal anchor stop transfer signal anchor stop transfer 27 Membrane Insertion of Type I TM Proteins - N-terminus in ER pore plug 28 Membrane Insertion of Proteins with an Internal Signal Anchor -N + + C -C α + + -N 29 Membrane Insertion of a Polytopic Membrane Protein gap 30 Post-translational Translocation of Proteins into the ER             31 BCH 444 Spring 2014 •  Targeting nascent proteins to the endoplasmic reticulum •  Protein translocation into the ER, membrane protein topology •  Protein glycosylation, functions of glycoproteins •  Protein folding in the ER, role of chaperones and folding catalysts •  Protein quality control - ERAD and the UPR David B. Williams, Room 5316 MSB david.williams@utoronto.ca 32 Protein Glycosylation in Eukaryotic Cells Ref: Essentials of Glycobiology www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=glyco2 Glycoproteins are typically classified according to the linkage between the amino acid and the first sugar in the oligosaccharide chain. Can be a bit confusing because more than one linkage can exist in a glycoprotein. Some common classes of glycoproteins: Glycoprotein class Linkage type Comments                 Abbreviations GlcNAc: N-acetyl glucosamine Man: Mannose Fuc: Fucose Glc: Glucose GalNAc: Gal: SA/NeuAc: N-acetyl galactosamine Galactose Sialic acid 33 O-linkage and oligosaccharide structures linkages between sugars These oligosaccharides are assembled stepwise by the addition of single sugars one-at-a-time through the action of glycosyltransferase enzymes. Initial addition of GalNAc to Ser/Thr occurs in the Golgi and further extension also occurs in this organelle. 34 N-linkage and oligosaccharide structures -P-P-dolichol Glcα1-2Glcα1-3Glcα1-3 Glc3Man9GlcNAc2-PP-dolichol Preassembled precursor oligosaccharide linked to a lipid carrier (dolichol) that resides in the ER membrane. It is transferred as a complete unit to Asn residues during nascent protein translocation into the ER, i.e., co-translationally. All N-linked oligosaccharides have a common core structure of Man3GlcNAc2 This is due to the fact that they are made from a common precursor within the ER 35 Oligosaccharides on glycoproteins are assembled by glycosyltransferases Acceptor Donor Reaction is driven by hydrolysis of phosphate bond from XDP-sugar GlcNAc transferase Disaccharide product 36 Properties of glycosyltransferases 1)  Typically very specific for both nucleotide sugar...
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