The role of lipids in the biogenesis of integral membrane proteins

Abstract

Most integral membrane proteins are cotranslationally inserted into the lipid bilayer. In prokaryotes, membrane insertion of the nascent chain takes place at the plasma membrane, whereas in eukaryotes insertion takes place into the endoplasmatic reticulum. In both kingdoms of life, however, the same membrane that acquaints the newly born membrane protein also synthesizes the bilayer lipids and thus ensures the balanced growth of the membrane as a whole. Recent evidence indicates that the lipid composition of the host membrane can determine the fate of the newborn membrane protein, as it can affect (1) the efficiency of translocation, (2) the topology of the resulting membrane protein, (3) its stability, (4) its assembly into oligomeric complexes, (5) its transport and sorting along the secretory pathway, and (6) its enzymatic activity. The lipid composition of the membrane thus can affect the biogenesis and function of integral membrane proteins at multiple steps along its biogenetic pathway. While understanding this interdependence between bilayer lipids and protein biogenesis is interesting in its own right, careful consideration of a potential host's membrane lipid composition may also allow optimization of the yield and activity of membrane proteins that are expressed in a heterologous organism. Here, we review and discuss some examples that illustrate the interdependence between bilayer lipids and the biogenesis of integral membrane proteins.

Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast

“…Recent studies on the protonpumping H 1 -ATPase, Pma1, reveal some of these functions (90). Pma1 has been a valuable model for determining how proteins are transported from the ER to the plasma membrane, and readers are directed to published reviews for more detailed information (91,92). Like all integral membrane proteins, Pma1 becomes part of the hydrophobic membrane in the ER, where lipids must contribute to the microenvironment necessary for the correct folding of Pma1 into a functional conformation.…”

Changes in Listeria monocytogenes Membrane Fluidity in Response to Temperature Stress

“…This occurs to maintain constant membrane fluidity. As the temperature decreases, the lipids found in the cell membrane become more rigid, which interferes with the activity of the membrane and membranebound components like channels and pumps (27,29). To the best of our knowledge, the time required for various Listeria monocytogenes strains to adjust their membrane fluidity is unknown.…”

“…When L. monocytogenes is grown at low temperatures, the phospholipids of the cell membrane become more rigid and can interfere with normal functions of the membrane and membrane-associated proteins (23,29,32,34). To counteract this phenomenon, L. monocytogenes modifies its plasma membrane to maintain its fluidity at low temperature (32); this is collectively termed homeoviscous adaptation (30).…”

Influence of lipids on protein-mediated transmembrane transport

“…Membrane proteins require an appropriate lipid environment for their structural integrity and in some cases for their correct insertion and possibly oligomeric state (Schneiter and Toulmay, 2007). From an organism's point of view, this is the strongest dependence on lipids because without the functional protein there would be no transport at all.…”