Structure Topology Prediction of Discriminative Sequence Motifs in Membrane Proteins with Domains of Unknown Functions

Steffen Grunert,Florian Heinke,Dirk Labudde

doi:10.1155/2013/249234

Abstract

Motivation. Membrane proteins play essential roles in cellular processes of organisms. Photosynthesis, transport of ions and small molecules, signal transduction, and light harvesting are examples of processes which are realised by membrane proteins and contribute to a cell's specificity and functionality. The analysis of membrane proteins has shown to be an important part in the understanding of complex biological processes. Genome-wide investigations of membrane proteins have revealed a large number of short, distinct sequence motifs.Results. The in silico analysis of 32 membrane protein families with domains of unknown functions discussed in this study led to a novel approach which describes the separation of motifs by residue-specific distributions. Based on these distributions, the topology structure of the majority of motifs in hypothesised membrane proteins with unknown topology can be predicted.Conclusion. We hypothesise that short sequence motifs can be separated into structure-forming motifs on the one hand, as such motifs show high prediction accuracy in all investigated protein families. This points to their general importance inα-helical membrane protein structure formation and interaction mediation. On the other hand, motifs which show high prediction accuracies only in certain families can be classified as functionally important and relevant for family-specific functional characteristics.

Highlights

Membrane proteins are essential for many fundamental biological processes within organisms
The in silico analysis of 32 membrane protein families with domains of unknown functions discussed in this study led to a novel approach which describes the separation of motifs by residue-specific distributions
We hypothesise that short sequence motifs can be separated into structure-forming motifs on the one hand, as such motifs show high prediction accuracy in all investigated protein families

Summary

Introduction

Membrane proteins are essential for many fundamental biological processes within organisms. Signal and energy transduction, and ion flow are only a few of the numerous functions enabled by membrane proteins [1]. Membrane proteins obtain their specific functionality by individual folding and interactions with the hydrophobic membrane environment as well as, in many cases, by oligomeric complex formation and protein-protein interactions [1, 2]. The identification of such complexes and interactions is valuable, since, on the one hand, detailed information of the function of an unknown membrane protein can be obtained by analysing its interactions with proteins of known function. Destabilisation of the three-dimensional structure of a membrane protein caused by mutations or ligand interactions are triggers for numerous diseases, for example, diabetes insipidus, cystic fibrosis, hereditary deafness and retinitis pigmentosa [5,6,7]

Methods

Results

Conclusion