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Structure-based statistical analysis of transmembrane helices

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Abstract

Recent advances in determination of the high-resolution structure of membrane proteins now enable analysis of the main features of amino acids in transmembrane (TM) segments in comparison with amino acids in water-soluble helices. In this work, we conducted a large-scale analysis of the prevalent locations of amino acids by using a data set of 170 structures of integral membrane proteins obtained from the MPtopo database and 930 structures of water-soluble helical proteins obtained from the protein data bank. Large hydrophobic amino acids (Leu, Val, Ile, and Phe) plus Gly were clearly prevalent in TM helices whereas polar amino acids (Glu, Lys, Asp, Arg, and Gln) were less frequent in this type of helix. The distribution of amino acids along TM helices was also examined. As expected, hydrophobic and slightly polar amino acids are commonly found in the hydrophobic core of the membrane whereas aromatic (Trp and Tyr), Pro, and the hydrophilic amino acids (Asn, His, and Gln) occur more frequently in the interface regions. Charged amino acids are also statistically prevalent outside the hydrophobic core of the membrane, and whereas acidic amino acids are frequently found at both cytoplasmic and extra-cytoplasmic interfaces, basic amino acids cluster at the cytoplasmic interface. These results strongly support the experimentally demonstrated biased distribution of positively charged amino acids (that is, the so-called the positive-inside rule) with structural data.

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Acknowledgments

This work was supported by grants BFU2009-08401 (to I.M.) and BFU2010-19310 (to M.A.M-R.) from the Spanish Ministry of Science and Innovation (MICINN, ERDF supported by the European Union), and by PROMETEO/2010/005 and ACOMP/2012/226 (to I.M.) and ACOMP/2011/048 (to M.A.M-R.) from the Generalitat Valenciana. C.B–D. was recipient of a predoctoral FPI fellowship from the MICINN.

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Authors and Affiliations

  1. Departament de Bioquímica i Biologia Molecular, Universitat de València, Burjassot, Spain

    Carlos Baeza-Delgado & Ismael Mingarro

  2. Structural Genomics Team, Genome Biology Group, National Center for Genomic Analysis (CNAG), Barcelona, Spain

    Marc A. Marti-Renom

  3. Structural Genomics Group, Center for Genomic Regulation (CRG), Barcelona, Spain

    Marc A. Marti-Renom

Authors
  1. Carlos Baeza-Delgado
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  2. Marc A. Marti-Renom
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  3. Ismael Mingarro
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Corresponding authors

Correspondence to Marc A. Marti-Renom or Ismael Mingarro.

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Special issue: Structure, function, folding and assembly of membrane proteins—Insight from Biophysics.

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Baeza-Delgado, C., Marti-Renom, M.A. & Mingarro, I. Structure-based statistical analysis of transmembrane helices. Eur Biophys J 42, 199–207 (2013). https://doi.org/10.1007/s00249-012-0813-9

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  • DOI: https://doi.org/10.1007/s00249-012-0813-9

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