A periodicity analysis of transmembrane helices

Transmembrane helices and the helical bundles which they form are the major building blocks of membrane proteins. Since helices are characterized by a given periodicity, it is possible to search for patterns of traits which typify one side of the helix and not the other (e.g. amphipathic helices contain a polar and apolar sides). Using Fourier transformation we have analyzed solved membrane protein structures as well as sequences of membrane proteins from the Swiss-Prot database. The traits searched included aromaticity, volume and ionization. While a number of motifs were already recognized in the literature, many were not. One particular example involved helix VII of lactose permease which contains seven aromatic residues on six helical turns. Similarly six glycine residues in four consecutive helical turns were identified as forming a motif in the chloride channel. A tabulation of all the findings is presented as well as a possible rationalization of the function of the motif.

[1]  Stefan Fischer,et al.  Translocation mechanism of long sugar chains across the maltoporin membrane channel. , 2002, Structure.

[2]  D. Engelman,et al.  Structure-based prediction of the stability of transmembrane helix-helix interactions: the sequence dependence of glycophorin A dimerization. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[3]  H Luecke,et al.  Structure of bacteriorhodopsin at 1.55 A resolution. , 1999, Journal of molecular biology.

[4]  J. Andersen,et al.  Importance of Stalk Segment S5 for Intramolecular Communication in the Sarcoplasmic Reticulum Ca2+-ATPase* , 2000, The Journal of Biological Chemistry.

[5]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[6]  M. Gerstein,et al.  Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with beta-branched residues at neighboring positions. , 2000, Journal of molecular biology.

[7]  David Eisenberg,et al.  GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles. , 2002, Biochemistry.

[8]  David Eisenberg,et al.  GXXXG and AXXXA: Common α-Helical Interaction Motifs in Proteins, Particularly in Extremophiles† , 2002 .

[9]  D. Engelman,et al.  A dimerization motif for transmembrane α–helices , 1994, Nature Structural Biology.

[10]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[11]  A T Brünger,et al.  A dimerization motif for transmembrane alpha-helices. , 1994, Nature structural biology.

[12]  H. Kaback,et al.  Site-directed sulfhydryl labeling of the lactose permease of Escherichia coli: helix VII. , 2000, Biochemistry.

[13]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.

[14]  R. Dutzler,et al.  X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity , 2002, Nature.

[15]  T. Tomizaki,et al.  The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.8 Å , 1996, Science.

[16]  Masayoshi Nakasako,et al.  Crystal structure of the calcium pump of sarcoplasmic reticulum at , 2000 .

[17]  T. Tomizaki,et al.  Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase. , 1998, Science.

[18]  D. Engelman,et al.  Motifs of serine and threonine can drive association of transmembrane helices. , 2002, Journal of molecular biology.

[19]  B. Persson,et al.  Cysteine-scanning mutagenesis of putative helix VII in the lactose permease of Escherichia coli. , 1993, Biochemistry.

[20]  H. Kaback,et al.  Cysteine scanning mutagenesis of putative helix XI in the lactose permease of Escherichia coli. , 1993, Biochemistry.

[21]  M. Kosloff,et al.  Structural homology discloses a bifunctional structural motif at the N-termini of Gα proteins , 2002 .

[22]  Sung-Hou Kim,et al.  Electron transfer by domain movement in cytochrome bc1 , 1998, Nature.

[23]  D. Engelman,et al.  TOXCAT: a measure of transmembrane helix association in a biological membrane. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. Phoenix,et al.  The hydrophobic moment and its use in the classification of amphiphilic structures (Review) , 2002, Molecular membrane biology.

[25]  I. Arkin,et al.  Experimental Measurement of the Strength of a Cα−H···O Bond in a Lipid Bilayer , 2004 .

[26]  S. Iwata,et al.  Structure and Mechanism of the Lactose Permease of Escherichia coli , 2003, Science.

[27]  E. Leberer,et al.  Functional consequences of glutamate, aspartate, glutamine, and asparagine mutations in the stalk sector of the Ca2+-ATPase of sarcoplasmic reticulum. , 1989, The Journal of biological chemistry.

[28]  David Eisenberg,et al.  GXXXG and GXXXA motifs stabilize FAD and NAD(P)-binding Rossmann folds through C(alpha)-H... O hydrogen bonds and van der waals interactions. , 2002, Journal of molecular biology.

[29]  Erik L. L. Sonnhammer,et al.  A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences , 1998, ISMB.

[30]  A. Brunger,et al.  Statistical analysis of predicted transmembrane alpha-helices. , 1998, Biochimica et biophysica acta.

[31]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1977, Journal of molecular biology.

[32]  K. Schulten,et al.  The crystal structure of the light-harvesting complex II (B800-850) from Rhodospirillum molischianum. , 1996, Structure.

[33]  A. Brunger,et al.  Statistical analysis of predicted transmembrane α-helices , 1998 .

[34]  D. Eisenberg,et al.  The hydrophobic moment detects periodicity in protein hydrophobicity. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[35]  W. Hubbell,et al.  Site-directed spin-labeling of transmembrane domain VII and the 4B1 antibody epitope in the lactose permease of Escherichia coli. , 1997, Biochemistry.

[36]  H. Kaback,et al.  Site-directed sulfhydryl labeling of the lactose permease of Escherichia coli: helix X. , 2000, Biochemistry.

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

[38]  C. DeLisi,et al.  Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. , 1987, Journal of molecular biology.

[39]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[40]  D. Engelman,et al.  The GxxxG motif: a framework for transmembrane helix-helix association. , 2000, Journal of molecular biology.

[41]  Maria Jesus Martin,et al.  The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003 , 2003, Nucleic Acids Res..

[42]  H. Kaback,et al.  Structure and mechanism of the lactose permease. , 2005, Comptes rendus biologies.

[43]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[44]  M. Nakasako,et al.  Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution , 2000, Nature.

[45]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[46]  J. Andersen,et al.  Mutation Lys758 → Ile of the Sarcoplasmic Reticulum Ca2+-ATPase Enhances Dephosphorylation ofE 2 P and Inhibits theE 2 to E 1Ca2Transition* , 1997, The Journal of Biological Chemistry.

[47]  S. O. Smith,et al.  Helix packing in polytopic membrane proteins: role of glycine in transmembrane helix association. , 1999, Biophysical journal.