Insight into recognition between aminoacyl carrier protein and its binding partner

Abstract

Acyl carrier-protein (ACP) is one of the most promiscuous protein in terms of protein-protein interactions within the cell. Common to both, primary and secondary cell metabolic pathways, ACP acts as a central acceptor of various intermediate products of fatty acid, polyketide and nonribosomal peptide synthesis pathways. Thus, it's quite puzzling how ACP selects correct protein partner among many possible upstream and downstream binding partners. To address this question we choose recently described protein-protein complex formed between aminoacyl carrier protein from Bradyrhizobium japonicum (Bj CP) and Bj Gly:CP ligase 1. We performed molecular dynamics simulations, MM-GBSA binding free energy calculations, alanine scanning mutagenesis, and multiple sequence alignment to get deeper insight into relevant protein-protein interactions between three forms of the aminoacyl carrier protein and their partner protein Bj Gly:CP ligase 1. Our result are in line with experimental findings and indicate that correct protein-protein communication is regulated through specific non-polar contribution of the interacting amino acid residues placed at the interface between aminoacyl carrier protein and partner Bj Gly:CP ligase 1. In silico alanine scanning mutagenesis along with multiple sequence alignment aided in classifying interacting residues as universally required for aminoacyl carrier protein binding and those that determine the selectivity.