Download STRUCTURES OF TYPICAL INTEGRAL MEMBRANE PROTEINS

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