Journal
ACS CHEMICAL BIOLOGY
Volume 4, Issue 11, Pages 895-909Publisher
AMER CHEMICAL SOC
DOI: 10.1021/cb900163d
Keywords
Biogenic membrane; Flippase; Flipping; Membrane protein; Polar lipid
Categories
Funding
- NIGMS NIH HHS [R01 GM071041, R01 GM071041-04, GM71041] Funding Source: Medline
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The biosynthesis of glycoconjugates such as N-glycoproteins and GPI-anchored proteins In eukaryotes and cell wall peptidoglycan and lipopolysaccharide in bacteria requires lipid intermediates to be flipped rapidly across the endoplasmic reticulum or bacterial cytoplasmic membrane (so-called biogenic membranes). Rapid flipping is also required to normalize the number of glycerophospholipids in the two leaflets of the bilayer as the membrane expands in a growing cell. Although lipids diffuse rapidly in the plane of the membrane, the Intrinsic rate at which they flip across membranes Is, very low, Biogenic membranes possess dedicated lipid transporters or flippases to increase flipping to a physiologically sufficient rate. The flippases are ATP-independent and facilitate downhill transport. Most predicted biogenic membrane flippases have not been identified at the molecular level; and the few flippases that have been Identified by genetic approaches have not been biochemically validated, Here we summarize recent progress on this fundamental topic and speculate on the mechanism(s) by which biogenic membrane flippases facilitate transbilayer lipid movement.
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