Artificial Neural Network for the Prediction of Tyrosine-Based Sorting Signal Recognition by Adaptor Complexes

[摘要] 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 byμ-subunits of the four clathrin-associated adaptor complexes (AP-1 to AP-4). Despite their overlap in specificity, eachμ-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 predicta priori, the specificity of a given tyrosine-signal for a particularμ-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-μinteractions with accuracies over 90%. Therefore, this approach constitutes a powerful tool to help predict mechanisms of intracellular protein sorting.

[学科分类] 基础医学