Has the code for protein translocation been broken?

Polypeptides chains are segregated by the translocon channel into secreted or membrane-inserted proteins. Recent reports claim that an in vivo system has been used to break the "amino acid code" used by translocons to make the determination of protein type (i.e. secreted or membrane-inserted). However, the experimental setup used in these studies could have confused the derivation of this code, in particular for polar amino acids. These residues are likely to undergo stabilizing interactions with other protein components in the experiment, shielding them from direct contact with the inhospitable membrane. Hence, it is our view that the "code" for protein translocation has not yet been deciphered and that further experiments are required for teasing apart the various energetic factors contributing to protein translocation.

[1]  T. Rapoport,et al.  Protein translocation by the Sec61/SecY channel. , 2005, Annual review of cell and developmental biology.

[2]  G. Heijne,et al.  Recognition of transmembrane helices by the endoplasmic reticulum translocon , 2005, Nature.

[3]  T. Date,et al.  Leader peptidase is found in both the inner and outer membranes of Escherichia coli. , 1981, The Journal of biological chemistry.

[4]  B. Bechinger Understanding peptide interactions with the lipid bilayer: a guide to membrane protein engineering. , 2000, Current opinion in chemical biology.

[5]  M. Cadene,et al.  X-ray structure of a voltage-dependent K+ channel , 2003, Nature.

[6]  D Eisenberg,et al.  Hydrophobicity and amphiphilicity in protein structure , 1986, Journal of cellular biochemistry.

[7]  T. Stevens,et al.  Are membrane proteins “inside‐out” proteins? , 1999, Proteins.

[8]  D. Engelman,et al.  Sequence motifs, polar interactions and conformational changes in helical membrane proteins. , 2003, Current opinion in structural biology.

[9]  Gunnar von Heijne,et al.  Transmembrane helices before, during, and after insertion. , 2005, Current opinion in structural biology.

[10]  Sarel J Fleishman,et al.  A novel scoring function for predicting the conformations of tightly packed pairs of transmembrane alpha-helices. , 2002, Journal of molecular biology.

[11]  Nir Ben-Tal,et al.  Free Energy Determinants of Peptide Association with Lipid Bilayers. , 2002 .

[12]  G. von Heijne,et al.  Interface connections of a transmembrane voltage sensor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  S. White,et al.  Membrane protein folding and stability: physical principles. , 1999, Annual review of biophysics and biomolecular structure.

[14]  T. Steitz,et al.  Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. , 1986, Annual review of biophysics and biophysical chemistry.

[15]  Youxing Jiang,et al.  Functional analysis of an archaebacterial voltage-dependent K+ channel , 2003, Nature.

[16]  E. Campbell,et al.  Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel , 2005, Science.

[17]  A charged view of voltage-gated ion channels , 2003, Nature Structural Biology.

[18]  Robert D. Lemon,et al.  Border Crossing , 2021 .

[19]  A. Kernytsky,et al.  Transmembrane helix predictions revisited , 2002, Protein science : a publication of the Protein Society.

[20]  W. Gullick,et al.  Neu receptor dimerization , 1989, Nature.

[21]  Duan Yang,et al.  Side-chain contributions to membrane protein structure and stability. , 2004, Journal of molecular biology.

[22]  Horst Wallrabe,et al.  Imaging protein molecules using FRET and FLIM microscopy. , 2005, Current opinion in biotechnology.

[23]  M. Tanouye,et al.  The size of gating charge in wild-type and mutant Shaker potassium channels. , 1992, Science.

[24]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[25]  W. Cramer,et al.  Membrane protein structure prediction: cytochrome b. , 1991, Trends in biochemical sciences.

[26]  G. Heijne Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. , 1992, Journal of molecular biology.

[27]  Gunnar von Heijne,et al.  Membrane Insertion of a Potassium-Channel Voltage Sensor , 2005, Science.

[28]  G von Heijne,et al.  Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. , 1992, Journal of molecular biology.

[29]  A. Ben-Shaul,et al.  A molecular model for lipid-protein interaction in membranes: the role of hydrophobic mismatch. , 1993, Biophysical journal.