How hydrophobic is alanine?
By a number of measures, alanine is poised at the threshold between those amino acids that promote the membrane integration of transmembrane alpha-helices and those that do not. We have measured the preference of alanine to partition into the lipid-water interface region over the central acyl chain region of the endoplasmic reticulum (ER) membrane both by its ability to promote the formation of so-called helical hairpins, i.e. a pair of transmembrane helices separated by a tight turn, and by mapping the position relative to the membrane of the lumenal end of a transmembrane alpha-helix that ends with a block of 10 alanines. Both measures show that Ala has a weak but distinct preference for the interface region, which is in agreement with recent biophysical measurements on pentaeptide partitioning in simple water-lipid or water-octanol systems (Jayasinghe, S., Hristova, K., and White, S. H. (2001) J. Mol. Biol. 312, 927-934). Considering the complexity of the translocon-mediated insertion of membrane proteins into the ER, the agreement between the biochemical and biophysical measurements is striking and suggests that protein-lipid interactions are already important during the very early steps of membrane protein assembly in the ER.
Nilsson
IngMarie
I
Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
Johnson
Arthur E
AE
von Heijne
Gunnar
G
D000409:Alanine / Q000737:chemistry*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D007930:Leucine / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins; D016297:Mutagenesis, Site-Directed; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry; D014158:Transcription, Genetic; D014867:Water / Q000737:chemistry*
D008055:Lipids; D008565:Membrane Proteins; D014867:Water; D004247:DNA; D012697:Serine Endopeptidases; C026515:type I signal peptidase; D007930:Leucine; D000409:Alanine