Structural features of transmembrane helices

A total of 160 transmembrane helices of 15 non‐homologous high‐resolution X‐ray protein structures have been analyzed in respect of their structural features. The dihedral angles and hydrogen bonds of the helical sections that span the hydrophobic interior of the lipid bilayer have been investigated. The Ramachandran plot of protein channels and solute transporters exhibit a significant shift Δ (φ‐ and ψ‐angles) of Δ mean (+4.5° and −5.4°), compared to a reference group of 151 α‐helices of the same average length derived from water‐soluble globular proteins. At the C‐termini of transmembrane helices structural motifs equivalent to the Gly‐caps of helices in globular proteins have been found, with two third of the transmembrane Gly‐caps taking up a primary structure that is typically not found at helix termini exposed to a polar solvent. The structural particularities reported here are relevant for the three‐dimensional modelling of membrane protein structures.

[1]  P. Bork,et al.  On α-helices terminated by glycine , 1991 .

[2]  Boris Martinac,et al.  Open channel structure of MscL and the gating mechanism of mechanosensitive channels , 2002, Nature.

[3]  W R Taylor,et al.  A model recognition approach to the prediction of all-helical membrane protein structure and topology. , 1994, Biochemistry.

[4]  S. White,et al.  Protein folding in membranes: determining energetics of peptide-bilayer interactions. , 1998, Methods in enzymology.

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

[6]  David Thomas,et al.  A sequence and structural study of transmembrane helices , 2001, J. Comput. Aided Mol. Des..

[7]  R. Preissner,et al.  Occurrence of bifurcated three‐center hydrogen bonds in protpins , 1991, FEBS letters.

[8]  J. Thornton,et al.  Satisfying hydrogen bonding potential in proteins. , 1994, Journal of molecular biology.

[9]  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.

[10]  G. Millhauser,et al.  α and 310: The Split Personality of Polypeptide Helices , 1999 .

[11]  F. Cordes,et al.  Proline-induced distortions of transmembrane helices. , 2002, Journal of molecular biology.

[12]  Ian W. Davis,et al.  Structure validation by Cα geometry: ϕ,ψ and Cβ deviation , 2003, Proteins.

[13]  N. Ben-Tal,et al.  kPROT: a knowledge-based scale for the propensity of residue orientation in transmembrane segments. Application to membrane protein structure prediction. , 1999, Journal of molecular biology.

[14]  Z. Derewenda,et al.  The occurrence of C-H...O hydrogen bonds in proteins. , 1995, Journal of molecular biology.

[15]  H. Khorana,et al.  Requirement of Rigid-Body Motion of Transmembrane Helices for Light Activation of Rhodopsin , 1996, Science.

[16]  Ming-Ming Zhou.  Phosphothreonine recognition comes into focus , 2000, Nature Structural Biology.

[17]  G. Montelione,et al.  A banner year for membranes , 1999, Nature Structural Biology.

[18]  Irene T Weber,et al.  Geometric criteria of hydrogen bonds in proteins and identification of "bifurcated" hydrogen bonds. , 2002, Protein engineering.

[19]  C. Deutsch.  Potassium channel ontogeny. , 2002, Annual review of physiology.

[20]  Pinak Chakrabarti,et al.  C—H⋯O hydrogen bond involving proline residues in α-helices , 1998 .

[21]  P. Chakrabarti,et al.  Sequence and structure patterns in proteins from an analysis of the shortest helices: implications for helix nucleation. , 2003, Journal of molecular biology.

[22]  D. Rees,et al.  Breaching the Barrier , 2003, Science.

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

[24]  D. Engelman,et al.  Interhelical hydrogen bonding drives strong interactions in membrane proteins , 2000, Nature Structural Biology.

[25]  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.

[26]  D. Pal,et al.  The interrelationships of side-chain and main-chain conformations in proteins. , 2001, Progress in biophysics and molecular biology.

[27]  D. Engelman,et al.  Membrane protein folding and oligomerization: the two-stage model. , 1990, Biochemistry.

[28]  D. Engelman,et al.  Helical membrane protein folding, stability, and evolution. , 2000, Annual review of biochemistry.

[29]  Pavel Strop,et al.  Crystal Structure of Escherichia coli MscS, a Voltage-Modulated and Mechanosensitive Channel , 2002, Science.

[30]  Nivedita Borkakoti,et al.  Solvent-induced distortions and the curvature of α-helices , 1983, Nature.

[31]  I. Rigoutsos,et al.  Structural details (kinks and non-alpha conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors. , 2003, Nucleic acids research.

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

[33]  J. Ren,et al.  Transmembrane orientation of hydrophobic alpha-helices is regulated both by the relationship of helix length to bilayer thickness and by the cholesterol concentration. , 1997, Biochemistry.

[34]  Dieter Langosch,et al.  Interaction of transmembrane helices by a knobs‐into‐holes packing characteristic of soluble coiled coils , 1998, Proteins.

[35]  E. Pérez-Payá,et al.  Influence of proline residues in transmembrane helix packing. , 2004, Journal of molecular biology.

[36]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[37]  J U Bowie,et al.  Helix packing in membrane proteins. , 1997, Journal of molecular biology.

[38]  J. Killian,et al.  How proteins adapt to a membrane-water interface. , 2000, Trends in biochemical sciences.

[39]  Alessandro Senes,et al.  The Cα—H⋅⋅⋅O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  S. White,et al.  An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method. , 1999, Journal of molecular biology.

[41]  J. Ponder,et al.  Tertiary templates for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. , 1987, Journal of molecular biology.