title: Artificial neural network for the prediction of tyrosine-based sorting signal recognition by adaptor complexes.
abstract: Sorting of transmembrane proteins to various intracellular compartments depends on specific signals present within their cytosolic domains. Among these sorting signals, the tyrosine-based motif (YXXØ) is one of the best characterized and is recognized by μ-subunits of the four clathrin-associated adaptor complexes (AP-1 to AP-4). Despite their overlap in specificity, each μ-subunit has a distinct sequence preference dependent on the nature of the X-residues. Moreover, combinations of these residues exert cooperative or inhibitory effects towards interaction with the various APs. This complexity makes it impossible to predict a priori, the specificity of a given tyrosine-signal for a particular μ-subunit. Here, we describe the results obtained with a computational approach based on the Artificial Neural Network (ANN) paradigm that addresses the issue of tyrosine-signal specificity, enabling the prediction of YXXØ-μ interactions with accuracies over 90%. Therefore, this approach constitutes a powerful tool to help predict mechanisms of intracellular protein sorting.
authors.affiliation: Department of Biological Sciences, Purdue Center for Cancer Research and Center for Science of Information, 201 S University Street, Hansen Life Sciences Building, West Lafayette, IN 47907, USA.
authors.forename: Debarati
authors.initials: D
authors.lastname: Mukherjee
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Hanna
authors.forename: R Claudio
authors.initials: RC
authors.lastname: Aguilar
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D015233:Models, Statistical; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer; D021382:Protein Sorting Signals; D021122:Protein Subunits; D015203:Reproducibility of Results; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism*; D015003:Yeasts
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D021382:Protein Sorting Signals; D021122:Protein Subunits; D014443:Tyrosine