HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, L.-P. Articles by Deber, C. M. Search for Related Content PubMed PubMed Citation Articles by Liu, L.-P. Articles by Deber, C. M.

J Biol Chem, Vol. 273, Issue 37, 23645-23648, September 11, 1998

COMMUNICATION
Uncoupling Hydrophobicity and Helicity in Transmembrane Segments
-HELICAL PROPENSITIES OF THE AMINO ACIDS IN NON-POLAR ENVIRONMENTS^*

Li-Ping Liu and Charles M. Deber^§

From Structural Biology and Biochemistry, Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8 and the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada

	ABSTRACT

Top Abstract Introduction Materials & Methods Results & Discussion References

Although the chains of amino acids in proteins that span the membrane are demonstrably helical and hydrophobic, little attention has been paid toward addressing the range of helical propensities of individual amino acids in the non-polar environment of membranes. Because it is inappropriate to apply soluble protein-based structure prediction algorithms to membrane proteins, we have used de novo designed peptides (KKAAAXAAAAAXAAWAAXAAAKKKK-amide, where X indicates one of the 20 commonly occurring amino acids) that mimic a protein membrane-spanning domain to determine the -helical proclivity of each residue in the isotropic non-polar environment of n-butanol. Peptide helicities measured by circular dichroism spectroscopy were found to range from ₂₂₂ = 17,000 ° (Pro) to 38,800 ° (Ile) in n-butanol. The relative helicity of each amino acid is shown to be well correlated with its occurrence frequency in natural transmembrane segments, indicating that the helical propensity of individual residues in concert with their hydrophobicity may be a key determinant of the conformations of protein segments in membranes.

	INTRODUCTION

Top Abstract Introduction Materials & Methods Results & Discussion References

Membrane-spanning segments of proteins are overwhelmingly -helical (1-5). Previous studies of protein transmembrane (TM)¹ segments have therefore tended to regard their helicity as a given parameter and focused principally on their hydropathy properties (6, 7). Yet considering the array of residues occurring in TM domains, including those considered classically as helix breakers (i.e. Gly, Ile, Val, Thr, and Pro) in aqueous-based proteins, it appears unlikely that all residues will possess identical helical propensities in the membrane environment. Previous studies of peptide/protein secondary structures in aqueous solution indicate that individual amino acids have distinct conformational preferences (-helical and -sheet) that influence protein structure and folding (8-13). However, in membranes, fatty acyl chains of lipid molecules present a hydrophobic environment to embedded proteins, and consequently, protein folding in membranes is subject to different rules versus those governing proteins in the aqueous milieu (14-16). The need for such information has become more crucial, because the genomes of various organisms recently analyzed indicate that large proportions (20-40%) of the genes correspond to membrane proteins.

We have now examined this situation using a set of de novo designed Ala-based peptides. Features of these peptides mimic a prototypical single-spanning membrane domain with respect to length, hydrophobicity, and residue occurrence. An excellent correlation is found between the experimentally measured helicity in the non-polar phase and the occurring frequency of a given residue computed from a data base of native protein TM helices. These findings identify a novel pathway through which the amino acid composition of a membrane protein can assist its accommodation in a hydrophobic environment.

	MATERIALS AND METHODS

Top Abstract Introduction Materials & Methods Results & Discussion References

Peptide Synthesis-- Peptides were synthesized by the continuous flow Fmoc solid phase method (17). C termini of peptides were aminated after cleavage from NovaSyn KR 125 resin. Purification of peptides was carried out on a reverse-phase Vydac-C4 semi-preparative HPLC (10 × 250 mm, 300 Å), using a linear gradient of acetonitrile in 0.1% trifluoroacetic acid. Purified peptides were characterized by analytical HPLC, amino acid analysis, and mass spectrometry. The aggregation states of peptides were monitored by CD measurements and by size exclusion HPLC, from which it was found that through the concentration range of 5-250 µM, peptides remained monomeric in all experimental media. Concentrations of peptides were determined in triplicate through quantitative amino acid analysis using Ala recovery as the standard and BCA protein assay (enhanced protocol). Peptides were stored as solid powders at 20 °C. To avoid the complexity of synthesizing a multiple Cys-containing peptide, only the central X residue was substituted by Cys, and the other two X residues were replaced by Leu.

Spectroscopic Measurements-- CD measurements were performed on a Jasco-720 spectropolarimeter using a 1-mm path length quartz cell at 25 °C. Each spectrum was the average of four scans with buffer background subtracted. Curves reported are based on triplicate measurements; standard deviation is ± 1%. Peptide concentration was typically 30 µM in aqueous buffer and in n-butanol. The aqueous buffer was prepared from 10 mM Tris-HCl, 10 mM NaCl, pH 7.0.

	RESULTS AND DISCUSSION

Top Abstract Introduction Materials & Methods Results & Discussion References

De Novo Peptide Design-- The rationale for the design of the peptides used in the present study, of sequence KKAAAXAAAAAXAAWAAXAAAKKKK-amide (where X indicates one of the 20 commonly occurring amino acids) (17, 18), is given as follows: (i) The hydrophobic segment of peptide is comprised of 19 amino acids, which when folded into an -helical conformation is of sufficient length to span a phospholipid bilayer (19). (ii) Distributions of the three "guest" residues X have been designed to preserve both angular and longitudinal symmetry around the helix, thereby minimizing any bias from amphipathic character that may arise when X is a polar or charged residue. In addition, triple substitutions of guest residue X in the hydrophobic core serve to amplify the effect of guest replacements, ensuring that the spectroscopic measurements can detect their structural impact. (iii) Ala, the most appropriate background residue as demonstrated by previous studies (20, 21), was chosen as the "host" residue. (iv) A Trp residue was incorporated into the hydrophobic segment as a fluorescence probe to monitor characteristics of the local microenvironment. (v) Lys residues were added at N and C termini to enhance the water solubility of peptides, whereas the C terminus was aminated to eliminate potential electrostatic attractions that might occur inter- or intramolecularly.

The solubility of these peptides in a wide variety of media make it feasible to investigate and compare specifically the conformational preferences of each residue in aqueous buffer versus non-polar media. Because the only difference among the present peptides is the guest X residues, it is reasonable to assume that variations in peptide helicity can be interpreted as a manifestation of the propensity for each X amino acid to form an -helical structure in a specific environment.

Helical Propensities of Residues in Aqueous Solution versus Organic Solvents-- CD spectroscopy, which is sensitive to secondary structure of proteins and polypeptides in solution, was used to monitor the conformations of model peptides. In aqueous buffer, peptides formed partial or non-helical conformations as shown by ₂₂₂ data in Table I and CD spectra shown for selected peptides (Fig. 1A); a generally good correlation was obtained when comparing peptide helicities with P values predicted by Chou and Fasman (Fig. 1B) (8), as well as with those obtained in several experimental systems (9, 10, 12). Because this group of algorithms is based on data from water-based peptides and proteins, these results imply that the present peptide design is an appropriate model to derive the helix propensities of each amino acid. That the Asp peptide showed relatively high helical propensity in this series of peptides, as does the Glu peptide, may be due to the fact that salt bridges potentially formed between these residues and that the terminal Lys residues may extend and stabilize peptide helices. However, any such overestimation of helicity for these two peptides is probably minor, because fairly good correlation is obtained when plotting their helicity in aqueous solution versus the C.-F. P parameter (Fig. 1B).

View this table: [in this window] [in a new window]   Table I Helical-forming tendency of model peptides KKAAAXAAAAAXAAWAAXAAAKKKK-amide in nonpolar and aqueous media, and -helical preferences of amino acids derived from protein transmembrane segments 222nm in CD spectra is used as a measure of helicity. Values reported are based on triplicate measurements, with a standard deviation of ±1%. Peptide concentrations were 30 µM.

View larger version (18K): [in this window] [in a new window]   Fig. 1.   A, circular dichroism spectra of selected model peptides (KKAAAXAAAAAXAAWAAXAAAKKKK-amide) recorded in aqueous buffer. The peptides shown (X indicates Ala, Gly, Ile, Leu, Ser, or Thr) represent a diversity of residue hydrophobicity and side chain chemistry. Peptide concentrations were typically 30 µM. The aqueous buffer was prepared from 10 mM Tris-HCl, 10 mM NaCl, pH 7.0. Curves reported are based on triplicate measurements with a standard deviation of ±1%. B, correlation of peptide helicity in aqueous solution with the Chou-Fasman helix propensity parameter (P).

Organic solvents with dielectric constants between pure water and the hydrocarbon interior of biological membranes have been widely used to mimic the non-polar environments of membranes (22-25). To create a quasi-membranous yet homogenous (isotropic) environment and to eliminate the complexities involved in protein/peptide-lipid interfacial interaction (viz. partitioning, electrostatics), peptides were dissolved in n-butanol, a moderate non-polar solvent of dielectric constant 17.8 at 25 °C (26), and their CD spectra were recorded. n-Butanol was chosen as a membrane-mimetic environment on the basis that (i) it effectively dissolved all 20 peptides, and (ii) in comparison to iso-propanol, n-propanol, and iso-butanol, n-butanol produced only minimum background absorbance at the lower wavelength region (<200 nm) of the CD measurements. Experiments with selected peptides in the above four solvents demonstrated that the CD spectra for a given peptide were essentially superimposable, indicating that the measured ellipticity is a property largely determined by the amino acid sequence of a peptide in this set of related solvents. Similar results were obtained for alcohol-induced helix formation of melittin, where end point ellipticities were essentially independent of the alcohol used (27).

In contrast to results obtained in aqueous buffer, all peptides formed predominantly -helical conformations in n-butanol (Table I; spectra shown for selected peptides in Fig. 2A). CD spectra were found to be independent of peptide concentration over the range 7.5-120 µM (not shown), and thus the helicity differences observed among the peptides are not caused by their differential solubility but by their intrinsic propensities to form the -helical conformation in a non-polar environment.

View larger version (18K): [in this window] [in a new window]   Fig. 2.   A, circular dichroism spectra of selected model peptides (see Fig. 1 legend) recorded in pure n-butanol. The peptides shown are those where X indicates Ala, Gly, Ile, Leu, Ser, or Thr. Peptide concentrations were 30 µM. B, correlation of peptide helicity in n-butanol with the helix propensity parameter P(TM) derived from single-spanning membrane proteins (see "Results and Discussion" and Table I).

Aromatic residues are known to contribute specifically to CD spectra in regions ascribed to secondary structure (28). Although a Trp residue is incorporated at the midsegment of all peptides as an integral part of the host sequence, no specific bias or distortion of spectra was observed. However, in those peptides containing multiple aromatic residues (i.e. when X indicates Trp, Phe, and Tyr at guest positions), aromatic contributions may be amplified, as suggested by the "off-line" points observed for Trp, Phe, and Tyr peptides in Figs. 1B and 2B.

The observation that there is a wide range of helical preferences for individual amino acids (~35% drop from Ile to Glu, and ~56% drop from Ile to Pro) in n-butanol appears to be a direct function of the ability of the solvent to "solvate" a given side chain. For example, amino acids with relatively non-polar side chains (Ile, Leu, Val, Ala, Gly, and Phe) showed higher helical-forming tendency than those with polar and charged side chains. Comparing the value of ₂₂₂ of each peptide in aqueous buffer versus n-butanol, we found that there are drastic differences regarding the rank order of helical propensity for these residues in the two media (Table I). Environment is thus a key regulatory factor in determining the conformation adopted by a given protein sequence. As a further example, although Gly and Pro are among the most destabilizing residues of -helices in globular proteins and polypeptides (8-10, 29), they do display a considerable tendency to form -helices in membrane environments (see Table I). Li et al. (23) also found that in a membrane environment, suitably placed Pro tends to protect rather than break -helical structures. Based on these data, it should not be unexpected that one finds Gly and Pro quite commonly in native transmembrane helices, especially Pro in transporter proteins (30-32). Notably, Ser and Thr display a higher tendency to occur in TM helices than in aqueous-based helices. These residues can satisfy their hydrogen-binding capacity by forming H bonds with the carbonyl oxygen in the preceding turn of the -helix, permitting such residues to occur in helices buried within a hydrophobic milieu (33-35).

Implications of Residue Helical Propensities for Protein Transmembrane Segments-- Several workers have analyzed the membrane inclusion preference of individual amino acids based on known membrane proteins (36-38), analogous to the C.-F. algorithm for globular proteins (8); for example, Jones et al. (38) used a dynamic programming algorithm to provide a membrane topology model from single sequence information. To obtain a membrane-based predictor comparable with the conventional C.-F. P parameter, we converted the "log likelihood" parameter of Jones et al. (si) to: P(TM) = qi/pi, where P(TM), the preference of an individual amino acid for occurrence in a TM helix, is the ratio of qi, the relative frequency of occurrence of the amino acid i in a particular structural class, to pi, the relative frequency of occurrence of the amino acid i in all the sequences in the data set. The resulting values of P(TM) derived from the "helix middle" of single-spanning membrane proteins are listed in Table I. There is good correlation (r = 0.93 when Pro was excluded) between the ₂₂₂ (n-butanol) and the P(TM) (Fig. 2B).

Thus, rather than simple identification of highly hydrophobic segments in the primary sequences of membrane proteins, the uncoupling of hydrophobicity from helicity in transmembrane domains allows a clearer delineation as to where helices are highly probable as a function of both protein sequence and environment. The correspondence observed between the experimentally determined helical propensity for individual amino acids and their non-random occurring frequency in protein TM helices suggests that the high frequency of occurrence in membranes of residues such as Leu, Val, Ile, and Phe derives not only from their hydrophobicity but also from their intrinsic propensity to form the -helical conformation in the non-polar environments of membranes.

	FOOTNOTES

^* This work was supported in part by grants (to C. M. D.) from the Natural Sciences and Engineering Research Council of Canada and the Medical Research Council of Canada.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a Hospital for Sick Children Research Training Committee award.

^§ To whom correspondence should be addressed: Structural Biology & Biochemistry, Research Inst., Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada. Tel.: 416-813-5924; Fax: 416-813-5005; E-mail: deber{at}sickkids.on.ca.

The abbreviations used are: TM, transmembrane; C.-F., Chou-Fasman; Fmoc, 9-fluorenylmethoxycarbonyl; HPLC, high pressure liquid chromatography.

	REFERENCES

Top Abstract Introduction Materials & Methods Results & Discussion References

1. Cheng, A., van Hoek, A. N., Yeager, M., Verkman, A. S., and Mitra, A. K. (1997) Nature 387, 627-630[CrossRef][Medline] [Order article via Infotrieve]
2. Walz, T., Hirai, T., Murata, K., Heymann, J. B., Mitsuoka, K., Fujiyoshi, Y., Smith, B. L., Agre, P., and Engel, A. (1997) Nature 387, 624-627[CrossRef][Medline] [Order article via Infotrieve]
3. Picot, D., Loll, P. J., and Garavito, R. M. (1994) Nature 367, 243-249[CrossRef][Medline] [Order article via Infotrieve]
4. Kuhlbrandt, W., Wang, D. N., and Fujiyoshi, Y. (1994) Nature 367, 614-621[CrossRef][Medline] [Order article via Infotrieve]
5. Pebay-Peyroula, E., Rummel, G., Rosenbusch, J. P., and Landau, E. M. (1997) Science 277, 1676-1681[Abstract/Free Full Text]
6. Engelman, D. M., Steitz, T. A., and Goldman, A. (1986) Annu. Rev. Biophys. Biophys. Chem. 15, 321-353[CrossRef][Medline] [Order article via Infotrieve]
7. Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132[CrossRef][Medline] [Order article via Infotrieve]
8. Chou, P. Y., and Fasman, G. D. (1974) Biochemistry 13, 211-222[CrossRef][Medline] [Order article via Infotrieve]
9. Chakrabartty, A., Kortemme, T., and Baldwin, R. L. (1994) Protein Sci. 3, 843-852[Abstract]
10. Blaber, M., Zhang, X.-J., and Matthews, B. W. (1993) Science 260, 1637-1640[Abstract/Free Full Text]
11. Minor, D. L., Jr., and Kim, P. S. (1994) Nature 367, 660-663[CrossRef][Medline] [Order article via Infotrieve]
12. Munoz, V., and Serrano, L. (1994) Proteins 20, 301-311[CrossRef][Medline] [Order article via Infotrieve]
13. O'Neil, K. T., and DeGrado, W. F. (1990) Science 250, 646-651[Abstract/Free Full Text]
14. Chang, D. K., Chien, W. J., and Arunkumar, A. I. (1997) Biophys. J. 72, 554-566[Medline] [Order article via Infotrieve]
15. Kothekar, V., Mahajan, K., Raha, K., and Gupta, D. (1996) J. Biomol. Struct. Dyn. 14, 303-316[Medline] [Order article via Infotrieve]
16. Lee, S., Kiyota, T., Kunitake, T., Matsumoto, E., Yamashita, S., Anzai, K., and Sugihara, G. (1997) Biochemistry 36, 3782-3791[CrossRef][Medline] [Order article via Infotrieve]
17. Liu, L.-P., and Deber, C. M. (1997) Biochemistry 36, 5476-5482[CrossRef][Medline] [Order article via Infotrieve]
18. Liu, L.-P., Li, S.-C., Goto, N. K., and Deber, C. M. (1996) Biopolymers 39, 465-470[CrossRef][Medline] [Order article via Infotrieve]
19. Reithmeier, R. A. F. (1995) Curr. Opin. Struct. Biol. 5, 491-500[CrossRef][Medline] [Order article via Infotrieve]
20. Deber, C. M., and Li, S. C. (1995) Biopolymers 37, 295-318[CrossRef][Medline] [Order article via Infotrieve]
21. Li, S. C., and Deber, C. M. (1994) Nat. Struct. Biol. 1, 368-373[CrossRef][Medline] [Order article via Infotrieve]
22. Chung, L. A. (1997) Anal. Biochem. 248, 195-201[CrossRef][Medline] [Order article via Infotrieve]
23. Li, S.-C., Goto, N. K., Williams, K. A., and Deber, C. M. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6676-6681[Abstract/Free Full Text]
24. Ben-Efraim, I., Bach, D., and Shai, Y. (1993) Biochemistry 32, 2371-2377[CrossRef][Medline] [Order article via Infotrieve]
25. Vinogradova, O., Badola, P., Czerski, L., Sonnichsen, F. D., and Sanders, C. R. (1997) Biophys. J. 72, 2688-2701[Abstract/Free Full Text]
26. Lide, D. R. (1991) CRC Handbook of Chemistry and Physics, 72nd Ed., CRC Press, Inc., Boca Raton, FL
27. Hirota, N., Mizuno, K., and Goto, Y. (1998) J. Mol. Biol. 275, 365-378[CrossRef][Medline] [Order article via Infotrieve]
28. Chakrabartty, A., Kortemme, T., Padmanabhan, S., and Baldwin, R. L. (1993) Biochemistry 32, 5560-5565[CrossRef][Medline] [Order article via Infotrieve]
29. Altmann, K. H., Wojcik, J., Vasquez, M., and Scheraga, H. A. (1990) Biopolymers 30, 107-120[CrossRef][Medline] [Order article via Infotrieve]
30. Deber, C. M., Glibowicka, M., and Woolley, G. A. (1990) Biopolymers 29, 149-157[CrossRef][Medline] [Order article via Infotrieve]
31. Rao, J. K. M., and Argos, P. (1986) Biochim. Biophys. Acta 869, 197-214[CrossRef][Medline] [Order article via Infotrieve]
32. Brandl, C. J., Deber, R. B., Hsu, L. C., Woolley, G. A., Young, X. K., and Deber, C. M. (1988) Biopolymers 27, 1171-1182[CrossRef][Medline] [Order article via Infotrieve]
33. MacKenzie, K. R., Prestegard, J. H., and Engelman, D. M. (1997) Science 276, 131-133[Abstract/Free Full Text]
34. Engelman, D. M., and Steitz, T. A. (1981) Cell 23, 411-422[CrossRef][Medline] [Order article via Infotrieve]
35. Gary, T. M., and Matthews, B. W. (1984) J. Mol. Biol. 175, 75-81[CrossRef][Medline] [Order article via Infotrieve]
36. Landolt-Marticorena, C., Williams, K. A., Deber, C. M., and Reithmeier, R. A. (1993) J. Mol. Biol. 229, 602-608[CrossRef][Medline] [Order article via Infotrieve]
37. Taylor, W. R., Jones, D. T., and Green, N. M. (1994) Proteins 18, 281-294[CrossRef][Medline] [Order article via Infotrieve]
38. Jones, D. T., Taylor, W. R., and Thornton, J. M. (1994) Biochemistry 33, 3038-3049[CrossRef][Medline] [Order article via Infotrieve]

---

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				K. Koide, K. Ito, and Y. Akiyama Substrate Recognition and Binding by RseP, an Escherichia coli Intramembrane Protease J. Biol. Chem., April 11, 2008; 283(15): 9562 - 9570. [Abstract] [Full Text] [PDF]

				J. He, R. Eckert, T. Pharm, M. D. Simanian, C. Hu, D. K. Yarbrough, F. Qi, M. H. Anderson, and W. Shi Novel Synthetic Antimicrobial Peptides against Streptococcus mutans Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1351 - 1358. [Abstract] [Full Text] [PDF]

				S. Esteban-Martin and J. Salgado Self-Assembling of Peptide/Membrane Complexes by Atomistic Molecular Dynamics Simulations Biophys. J., February 1, 2007; 92(3): 903 - 912. [Abstract] [Full Text] [PDF]

				J. Ding, J. K. Rainey, C. Xu, B. D. Sykes, and L. Fliegel Structural and Functional Characterization of Transmembrane Segment VII of the Na+/H+ Exchanger Isoform 1 J. Biol. Chem., October 6, 2006; 281(40): 29817 - 29829. [Abstract] [Full Text] [PDF]

				E. Glukhov, M. Stark, L. L. Burrows, and C. M. Deber Basis for Selectivity of Cationic Antimicrobial Peptides for Bacterial Versus Mammalian Membranes J. Biol. Chem., October 7, 2005; 280(40): 33960 - 33967. [Abstract] [Full Text] [PDF]

				M. Y. Choi, A. W. Partridge, C. Daniels, K. Du, G. L. Lukacs, and C. M. Deber Destabilization of the Transmembrane Domain Induces Misfolding in a Phenotypic Mutant of Cystic Fibrosis Transmembrane Conductance Regulator J. Biol. Chem., February 11, 2005; 280(6): 4968 - 4974. [Abstract] [Full Text] [PDF]

				M. W. Hofmann, K. Weise, J. Ollesch, P. Agrawal, H. Stalz, W. Stelzer, F. Hulsbergen, H. de Groot, K. Gerwert, J. Reed, et al. De novo design of conformationally flexible transmembrane peptides driving membrane fusion PNAS, October 12, 2004; 101(41): 14776 - 14781. [Abstract] [Full Text] [PDF]

				A. Caballero-Herrera and L. Nilsson Molecular Dynamics Simulations of the E1/E2 Transmembrane Domain of the Semliki Forest Virus Biophys. J., December 1, 2003; 85(6): 3646 - 3658. [Abstract] [Full Text] [PDF]

				W. F. DeGrado, H. Gratkowski, and J. D. Lear How do helix-helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo-oligomeric helical bundles Protein Sci., April 1, 2003; 12(4): 647 - 665. [Abstract] [Full Text] [PDF]

				V. M. Nappi, J. A. Schaefer, and L. M. Petti Molecular Examination of the Transmembrane Requirements of the Platelet-derived Growth Factor beta Receptor for a Productive Interaction with the Bovine Papillomavirus E5 Oncoprotein J. Biol. Chem., November 27, 2002; 277(49): 47149 - 47159. [Abstract] [Full Text] [PDF]

				M. J. De Rosa, D. Rayes, G. Spitzmaul, and C. Bouzat Nicotinic Receptor M3 Transmembrane Domain: Position 8' Contributes to Channel Gating Mol. Pharmacol., August 1, 2002; 62(2): 406 - 414. [Abstract] [Full Text] [PDF]

				W. Hosia, J. Johansson, and W. J. Griffiths Hydrogen/Deuterium Exchange and Aggregation of a Polyvaline and a Polyleucine {alpha}-Helix Investigated by Matrix-assisted Laser Desorption Ionization Mass Spectrometry Mol. Cell. Proteomics, August 1, 2002; 1(8): 592 - 597. [Abstract] [Full Text] [PDF]

				F.-X. Ding, D. Schreiber, N. C. VerBerkmoes, J. M. Becker, and F. Naider The Chain Length Dependence of Helix Formation of the Second Transmembrane Domain of a G Protein-coupled Receptor of Saccharomyces cerevisiae J. Biol. Chem., April 19, 2002; 277(17): 14483 - 14492. [Abstract] [Full Text] [PDF]

				C. M. Deber, C. Wang, L.-P. Liu, A. S. Prior, S. Agrawal, B. L. Muskat, and A. J. Cuticchia TM Finder: A prediction program for transmembrane protein segments using a combination of hydrophobicity and nonpolar phase helicity scales Protein Sci., January 1, 2001; 10(1): 212 - 219. [Abstract] [Full Text]

				Y. Kida, M. Sakaguchi, M. Fukuda, K. Mikoshiba, and K. Mihara Membrane Topogenesis of a Type I Signal-Anchor Protein, Mouse Synaptotagmin II, on the Endoplasmic Reticulum J. Cell Biol., August 21, 2000; 150(4): 719 - 730. [Abstract] [Full Text] [PDF]

				K. Rosch, D. Naeher, V. Laird, V. Goder, and M. Spiess The Topogenic Contribution of Uncharged Amino Acids on Signal Sequence Orientation in the Endoplasmic Reticulum J. Biol. Chem., May 12, 2000; 275(20): 14916 - 14922. [Abstract] [Full Text] [PDF]

				D. Langosch, B. Brosig, and R. Pipkorn Peptide Mimics of the Vesicular Stomatitis Virus G-protein Transmembrane Segment Drive Membrane Fusion in Vitro J. Biol. Chem., August 17, 2001; 276(34): 32016 - 32021. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, L.-P. Articles by Deber, C. M. Search for Related Content PubMed PubMed Citation Articles by Liu, L.-P. Articles by Deber, C. M.