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548th Meeting of the Biochemical Society The Queen’s University of Belfast, Belfast, 9 and 1 0 April 1974 INTERRELATIONSHIPS OF VIRUSES A N D MEMBRANES : a Colloquium organized by S. J. Martin (Belfast) The Structure of Cell Membranes MARK S. BRETSCHER MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U.K. Membranes are conventionally thought of as permeability barriers for compartmentalizing cellular processes. This is probably true of plasma, endoplasmic, Golgi, bacterial inner and mitochondria1 inner membranes. This is not true of bacterial outer membranes, which are probably not real membranes anyway. These former membranes can also serve a different purpose; they can be used to concentrate (hydrophobic) enzymes. This has a special advantage if these enzymes are mobile within one plane and can pass a product from one enzyme as a substrate for another enzyme. Such enzymes would be expected to be found associated only with the cytoplasmic side of a bilayer. This probably explains why there seems to be more protein associated with the cytoplasmic side of a membrane than there is with the external surface of the membrane. The corollary of this argument is that the external lipid monolayer is much more extensive than the cytoplasmic lipid monolayer in the bilayer leaflet of a membrane. This picture fits in well with our present scheme for the structure of membranes of higher organisms, which can be summarized as follows. (1) Choline phospholipids and glycolipids (which together usually make up the major portion of lipid) constitute the external monolayer, and amino phospholipids make up the cytoplasmic monolayer of a membrane bilayer. Lipid molecules do not spontaneously migrate from one side of the bilayer to the other. (2) Most membrane proteins are associated with the cytoplasmic side of the membrane only. (3) The remaining proteins extend across the bilayer (usually carrying out transport activities: either molecules, such as lactose by the lactose permease, or information, such as by the adenylate cyclase system). These proteins do not rotate across the membrane. Proteins are not usually associated exclusively with the external half of a bilayer. (4) All carbohydrate associated with membranes, whether as glycoprotein or glycolipid, is located on the external side of the bilayer. ( 5 ) Membrane proteins should be regarded as cytoplasmic proteins which are, by their nature, hydrophobic, and so spontaneously dissolve in the lipid bilayer. They are not proteins which got ‘stuck’ in the membrane by an abortive secretory process. VOl. 2