Proteins in both prokaryotic and eukaryotic cells have to find their way among a plethora of subcellular compartments. The targeting information in most cases resides in distinct stretches of amino acids or targeting peptides (TPs). The sequence characteristics of a number of different TPs have been defined by comparative sequence analysis and experimental studies. TPs targeting proteins for secretion, for import into mitochondria, and for import into chloroplasts will be reviewed, with particular emphasis on the patterns of amino acids that define their cleavage sites.
We show that the so‐called ‘positive inside’ rule, i.e. the observation that positively charged amino acids tend to be more prevalent in cytoplasmic than in extra‐cytoplasmic segments in transmembrane proteins [von Heijne, G. (1986) EMBO J. 5 , 3021–3027], seems to hold for all polar segments in multi‐spanning eukaryotic membrane proteins irrespective of their position in the sequence and hence can be used in conjunction with hydrophobicity analysis to predict their transmembrane topology. Further, as suggested by others, we confirm that the net charge difference across the first transmembrane segment correlates well with its orientation [Hartmann, E., Rapoport, T. A. and Lodish, H. F. (1989) Proc. Natl Acad. Sci. USA 86 , 5786–5790], and that the overall amino‐acid composition of long polar segments can also be used to prodict their cytoplasmic or extra‐cytoplasmic location [Nakashima, H. and Nishikawa, K. (1992) FEBS Lett. 303 , 141–146]. We present an approach to the topology prediction problem for eukaryotic membrane proteins based on a combination of these methods.
We report the development of LumenP, a new neural network-based predictor for the identification of proteins targeted to the thylakoid lumen of plant chloroplasts and prediction of their cleavage sites. When used together with the previously developed TargetP predictor, LumenP reaches a significantly better performance than what has been recorded for previous attempts at predicting thylakoid lumen location, mostly due to a lower false positive rate. The combination of TargetP and LumenP predicts around 1.5%-3% of all proteins encoded in the genomes of Arabidopsis thaliana and Oryza sativa to be located in the lumen of the thylakoid.
Primary structures of 250 characterized proteins with N‐terminally acetylated residues were correlated with residue distributions and other data. Excluding multiple forms derived from characterized species variants, the structures represent 105 different types of acetylated proteins. Results of comparisons extend previous suggestions based on fewer structures and define relationships further. The N‐terminal residue that is acetylated is of a limited type and is frequently a small residue, with a heavy over‐representation of serine and alanine. However, the occurrence of methionine at the acetylated position is also high, whereas that of glycine is less frequent than previously estimated. Lysine is over‐represented in the N‐terminal region, as is aspartic and glutamic acids at a few positions close to the acetylated N‐terminus (especially the adjacent position). Finally. distributions of branched‐chain residues in the N‐terminal region of acetylated proteins are altered in relation to those of proteins in general, isoleucine is over‐represented, and leucine and valine are under‐represented. The results suggest that α‐amino‐acetylated proteins have special residues in N‐terminally non‐hydrophobic structures. Data are compatible with a protective function for acetylation but do not exclude further role(s) in processing or other special functions.
A kinetic model for the helix-cruciform transition is presented, mean lifetimes for the cruciform states are calculated and shown to be inconsistent with the notion of metastability.
The subcellular location of a protein is an important characteristic with functional implications, and hence the problem of predicting subcellular localization from the amino acid sequence has received a fair amount of attention from the bioinformatics community. This review attempts to summarize the present state of the art in the field.
We have examined the effect of Trp and Phe residues on the positioning of a poly-Leu transmembrane helix relative to the microsomal membrane by employing a previously described "glycosylation mapping" technique [Nilsson, I. M., Sääf, A., Whitley, P., Gafvelin, G., Waller, C., and von Heijne, G. (1998) J. Mol. Biol. 284, 1165−1175]. Both Trp and Phe tend to push the transmembrane helix into the membrane when inserted in positions flanking the poly-Leu stretch, and Trp (but not Phe) pulls the transmembrane helix toward the lipid−water interface when inserted inside the poly-Leu segment. Thus, the preference of Trp for the lipid−water interface previously suggested on the basis of biophysical studies of model peptides can also be observed for a bona fide transmembrane helix in a biological membrane. We further show that a sufficiently long poly-Trp segment functions as an efficient stop-transfer sequence during protein translocation across the microsomal membrane, despite the preference of Trp residues for the lipid−water interface region.
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Conference Abstract| October 01 2000 Insertion of transmembrane helices into the ER membrane G. von Heijne G. von Heijne 1Dept. of Biochemistry, Stockholm University, S-10691 Stockholm, Sweden Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 2000 Biochemical Society2000 Biochem Soc Trans (2000) 28 (5): A116. https://doi.org/10.1042/bst028a116 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation G. von Heijne; Insertion of transmembrane helices into the ER membrane. Biochem Soc Trans 1 October 2000; 28 (5): A116. doi: https://doi.org/10.1042/bst028a116 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2000 Biochemical Society2000 Article PDF first page preview Close Modal You do not currently have access to this content.
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A comparative study of three kinds of eukaryotic N-terminal topogenic sequences, viz signal peptides, N-terminal transmembrane anchors, and mitochondrial targeting sequences, suggests: (1) that the sign of the N-terminal charge might influence the orientation of an N-terminal hydrophobic segment relative to the membrane and give rise to N-terminally anchored proteins with their main mass exposed either on the cytosolic or extra-cytosolic side of the membrane; and (2) that N-terminal transmembrane segments in mitochondrial targeting sequences have a relatively low overall hydrophobicity, probably in order to avoid being recognized by the endoplasmic reticulum export machinery.
