Peptides insertion into membrane

Step 2. The signal peptide inserts into the membrane. We propose that the polar c region of the signal sequence resides transiently in the aqueous region of the periplasmic or lumenal side of the membrane. 

Valincius et al. used NR and ex situ electrochemical impedance spectroscopy to study the effect of amyloid (J-pephde insertion on supported hpid bilayers [60]. It has been speculated that the interaction between these oligomeric proteins and bilayer membranes plays an important role in the aggregation and protein misfold-ing that leads to various neurodegenerahve diseases including Alzehimer s and Parkinson s diseases [61]. Using a variety of solvent and phospholipid contrasts, including the use of perdeuterated phosphohpids, NR demonstrated that amyloid P-peptides inserted into hpid bilayers tethered to a gold-modified silicon substrate. 

Signal hypothesis A mechanism proposed by Blobel for the segregation of secretory proteins during their biosynthesis. It has since been found applicable to most proteins which are either inserted into membranes or transported across them, including organelle proteins which are synthesized in the cytosol. Such proteins are transcribed with a signal or leader peptide of 15 to 30 amino acid residues About 70... 

Nearly all bacterial proteins are synthesized with a formyl-methionine as the first amino acid, as described above. Yet most proteins isolated from cell culture do not contain an N-terminal fMet or Met residue, indicating that the maturation process involves proteolytic removal of this amino acid. Some proteolytic events release a functional protein from a synthesized precursor, or proprotein. An example is insulin, which is released from its proinsulin precursor by excision of an internal 33-residue peptide. Another type of proteolytic processing is the removal of N-terminal signal peptides, which target some proteins for insertion into membranes or for secretion from the cell. 

The nuclear-encoded proteins are inserted into both inner and outer mitochondrial membranes, the intermembrane space, and the matrix and there are several different mechanisms involved. As mentioned above there is no apparent requirement for a presequence on proteins which insert specifically into the mitochondrial outer membrane. For proteins destined for the inner mitochondrial membrane, a stop-transfer mechanism is proposed. Thus some information in the peptide must stop the complete transfer of the protein into the mitochondrial matrix, enabling the protein to remain in the inner mitochondrial membrane. For some proteins in the intermembrane space (for example the Rieske iron-sulphur protein associated with the outer face of complex III), a particularly complicated import pathway... 

Brasseur R, Cornet B, Burny A, Vandenbranden M, Ruysschaert JM (1988) Mode of insertion into a lipid membrane of the N-terminal HIV gp41 peptide segment. AIDS Res Hum Retroviruses 4 83-90... 

The C-terminal hydrophobic region of the peptide has been suggested to insert into the lipid bilayer of the membrane, perhaps forming an a-helical structure after insertion [169, 174, 175]. 

Peptides may bind to a membrane either by association to its surface or by insertion into its interior. The latter class comprises the integral membrane proteins whose structures are largely a-helical or / -barrel type (see Chap. 12 in Ref. [32]). The topology of interaction of helices with membranes is displayed in Fig. 5.1. 

One experimental tool in this direction is provided by some enveloped animal viruses which mature at the cell surface of infected cells (K Sri inen and Renkonen, 1977 Lenard, 1978). Such viruses include influenza virus, Semliki Forest virus (SFV), Sindbis virus, and vesicular stomatitis virus (VSV). They are extremely simple in makeup and hence are very well characterized. They can be tagged with biochemical probes in many different ways. They infect many animal cells in culture, and after infection turn the cells into factories for the production of virus progeny. The protein-synthesizing machinery of the host cell is programmed by the viral RNA to make viral proteins exclusively and these include the viral surface glycoproteins. These are synthesized with signal peptides and inserted into the ER membrane (Katz et ai, 1977 Garoff et... 

The association of host defense peptides with lipid bilayers has been observed to be directly related to the ratio of peptide to lipid. At low peptide/lipid ratios, peptides are oriented parallel to the membrane. As the ratio increases, the peptides reorient themselves perpendicular to the membrane, ultimately inserting into the bilayer. Following membrane insertion transmembrane pores are formed. The insertion of peptides into the lipid membrane and subsequent translocation of peptides into the cytoplasm or formation of transmembrane pores has been described by multiple models of host defense peptide insertion. 

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