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STRUCTURES OF TYPICAL INTEGRAL MEMBRANE PROTEINS ! part of protein crosses hydrophobic region of the bilayer; typically as an α-helix 1. Glycophorin A ! human red blood cell membrane; no known function ! typical single-spanning membrane protein ! N-terminal region on outside surface; polar amino acids + attached carbohydrate chains ! stretch of 19 hydrophobic amino acids ! α-helical transmembrane segment ! C-terminal region inside cell; rich in charged amino acids 2. Bacteriorhodopsin ! in membrane of halophilic (salt-loving) bacterium ! light driven transporter; pumps H+ from cytosol to outside ! typical multi-spanning membrane protein ! has 7 α-helical transmembrane segments, connected by short loops ! arranged as a helix bundle, slightly tilted in membrane GLYCOLIPIDS AND GLYCOPROTEINS ! carbohydrate chains are found covalently attached to both lipids and proteins 1. Glycosphingolipids (GSL) ! sphingosine + N-acyl fatty acid = ceramide ! during biosynthesis, sugars added one at a time by glycosyltransferase enzymes Neutral GSL: contain uncharged sugars ! if add a single sugar as headgroup ! cerebroside β1-Gal ! galactocerebroside β1-Glc ! glucocerebroside ! complex GSL can have a chain of several sugars Acidic GSL - gangliosides: ! contain the 9C acidic sugar N-acetylneuraminic acid (sialic acid); !vely charged at pH 7 ! found in large amounts in brain e.g. ganglioside GM1 2. Glycoproteins ! two types of attached sugar chains N-linked chains: N-acetylglucosamine GlcNAc ! Asn side chain (!CO-NH2) O-linked chains: N-acetylgalactosamine GalNAc ! Ser/Thr side chain (!OH) ! sugar chains of glycoproteins and glycolipids form a thick layer, called glycocalyx, on outside surface of plasma membrane ! involved in cell surface recognition ! sugar chains important as receptors, surface antigens e.g. ganglioside GM1 is receptor for cholera toxin, allows subunit with toxic activity to enter cell BLOOD GROUP ANTIGENS ! carried on GSLs in plasma membrane of red blood cells ! also found on glycoproteins and glycolipids in other cells ! sugar chain has different structures, depending on blood type Type O Galβ1! O-antigen Type A GalNAc(α1!3)Galβ1! A-antigen Type B Gal(α1!3)Galβ1! B-antigen Type AB has both A type and B type antigens ! different structures arise from different variants (alleles) of a gene encoding a glycosyltransferase enzyme Type O Type A Type B inactive enzyme, does not add a sugar enzyme adds GalNAc enzyme adds Gal ! must be careful when transfusing blood, since naturallyoccurring autoantibodies exist in serum, which agglutinate red blood cells of different type e.g. blood of type A individuals has antibody to type B, cannot receive type B blood ! no-one has antibodies to type O blood; everyone can receive type O blood, universal donor