Signal peptide cleavage

Jain, R., Rusch, S., and Kendall, D. (1994). Signal peptide cleavage regions. Functional limits on length and topological implications./. Biol. Chem. 269, 16305-16310. 

Protein synthesis and folding Signal peptide cleavage Formation of disulfide bonds Oligomerization A/-Clycosylation folding... 

Figure 12.15. Prediction of signal peptide cleavage site. The profile plot shows the prediction of signal peptide cleavage site of duck lysozyme by SignalP.

Nielsen, H Engelbrecht, J., von Heijne, G. Brunak, S. (1996). Defining a similarity threshold for a functional protein sequence pattern the signal peptide cleavage site. Proteins 24,165-77. (The data set is available from the FTP server at ftp //virus.cbs.dm.dk/pub/signalp). 

The following example shows how BioPerl can be used to read protein sequences from a FASTA file and find signal peptide cleavage sites. The file format is inferred from the file extension. fa. 

Fig. 3.3 FVIII biosynthesis. Signal peptide cleavage and asparagine (N)-linked glycosylation of the FVIII occurs after translation and translocation to the lumen of the endoplasmic reticulum (ER). Within the ER, the FVIII is folded, which requires binding to chaperone proteins. FVIII binds immunoglobulin-binding protein (BiP) at the A1 domain, and is released in an ATP-dependent step. Next, FVIII binds calnexin (CNX) and calreticulin (CRT) (not shown) at the B domain. Properly folded FVIII proteins are transported to the Golgi by chaperone proteins, LMANl and MCFD2 (not shown) for further processing LMANl also binds to the FVIII B domain. Incorrectly folded FVIII...

Fig. 3. NMR structures of PrP-sen. The refined NMR structure of (A) recombinant mouse PrP-sen from amino acid residues 121-231 (Riek et al., 1996) and (B) recombinant hamster PrP-sen from amino acid residues 23-231 (Liu et al, 1999). The structure of full-length mouse PrP-sen has been derived (Riek et al., 1997), but residues from the signal peptide cleavage site to the structure illustrated (i.e., 23-120) exist in a flexible, random coil-like state as shown for the hamster PrP-sen structure in (B). S, P strand H, a helix. Figure prepared with the program MOLMOL (Koradi et al, 1996).

Technologies that offer the opportunity to use MS for intact protein mass determination allow rapid assessment of signal peptide cleavage sites and post-translational heterogeneity. A well-resolved mass spectrum of an intact protein defines its native covalent profile as well as its associated heterogeneity. A comprehensive mass spectrometric approach that integrates both intact protein molecular mass measurement (top-down) and proteolytic fragment identification (bottom-up) would represent a powerful approach for proteome/ protein characterization. 

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