Sequence and structural analysis of fibronectin-binding protein reveals importance of multiple intrinsic disordered tandem repeats.

The location of certain amino acid sequences like repeats along the polypeptide chain is very important in the context of forming the overall shape of the protein molecule which in fact determines its function. In gram-positive bacteria, fibronectin-binding protein (FnBP) is one such repeat containing protein, and it is a cell wall-attached protein responsible for various acute infections in human. Several studies on sequence, structure, and function of fibronectin-binding regions of FnBPs were reported; however, no detailed study was carried out on the full-length protein sequence. In the present study, we have made a thorough sequence and structure analysis on FnBP_A of Staphylococcus aureus and explored the presence of dual ligand-binding ability of fibrinogen (fg)-binding region and its molecular recognition processes. Multiple sequence alignment and protein-protein docking analysis reveal the regions which are likely involved in dual ligand binding. Further analysis of docking of FnBP_A fg-binding region and fn N-terminal modules suggests that if the latter binds to the fg-binding region of FnBP_A, it would inhibit the subsequent binding of fg because of steric hindrance. The sequence analysis further suggests that the abundance of disorder promoting residue glutamic acid and dual personality (both order/disorder promoting) residue threonine in tandem repeats of FnBP_A and B proteins possibly would help the molecule to undergo a conformational change while binding with fn by β-zipper mechanism. The segment-based power spectral analysis was carried out which helps to understand the distribution of hydrophobic residues along the sequence particularly in intrinsic disordered tandem repeats. The results presented here will help to understand the role of internal repeats and intrinsic disorder in the molecular recognition process of a pathogenic cell surface protein.