GPCRtm: An amino acid substitution matrix for the transmembrane region of class A G Protein-Coupled Receptors

BMC Bioinformatics

Research Article

Leonardo Pardo¹  Santiago Rios¹  Gianluigi Caltabiano¹  Marta F. Fernandez¹  Mercedes Campillo¹  Angel Gonzalez¹ 

[1] Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain;

关键词: Amino acid substitution matrix;    G protein-coupled receptors;    GPCR;    Transmembrane;    Evolution;    Membrane protein;   

DOI  :  10.1186/s12859-015-0639-4

 received in 2015-03-20, accepted in 2015-06-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundProtein sequence alignments and database search methods use standard scoring matrices calculated from amino acid substitution frequencies in general sets of proteins. These general-purpose matrices are not optimal to align accurately sequences with marked compositional biases, such as hydrophobic transmembrane regions found in membrane proteins. In this work, an amino acid substitution matrix (GPCRtm) is calculated for the membrane spanning segments of the G protein-coupled receptor (GPCR) rhodopsin family; one of the largest transmembrane protein family in humans with great importance in health and disease.ResultsThe GPCRtm matrix reveals the amino acid compositional bias distinctive of the GPCR rhodopsin family and differs from other standard substitution matrices. These membrane receptors, as expected, are characterized by a high content of hydrophobic residues with regard to globular proteins. On the other hand, the presence of polar and charged residues is higher than in average membrane proteins, displaying high frequencies of replacement within themselves.ConclusionsAnalysis of amino acid frequencies and values obtained from the GPCRtm matrix reveals patterns of residue replacements different from other standard substitution matrices. GPCRs prioritize the reactivity properties of the amino acids over their bulkiness in the transmembrane regions. A distinctive role is that charged and polar residues seem to evolve at different rates than other amino acids. This observation is related to the role of the transmembrane bundle in the binding of ligands, that in many cases involve electrostatic and hydrogen bond interactions. This new matrix can be useful in database search and for the construction of more accurate sequence alignments of GPCRs.

【 授权许可】

Unknown   
© Rios et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.