Introduction

Prosequences are stretches of amino acid translated along with protein, but are often removed from the mature protein later through excision. This is known to assist the three-dimensional folding of their cognate protein, and also prevents precocious activation and proteolytic degradation. Prosequences are also termed intramolecular chaperones, and the whole stretch of an initially translated polypeptide is termed a preproprotein. Preproproteins have so far been reported in at least 690 organisms including eukaryotes, archaea, bacteria and viruses, with most of them being present as N-terminal prosequences. The unique role of prosequences can be exploited for protein engineering but this requires a detailed understanding of the role of prosquences in cognate protein folding. In this study, we tried to explore the structural effect of prosequences on their cognate preproprotein.

Method

Structural homologs of N-terminal prosequence-containing proteins were retrieved from PDB-based similarity and coverage criteria. The RING webserver was used for predicting prosequence and protein interacting sites. The possible binding pockets were predicted using CASTp. Known ligand-binding sites were explored through Pdbsum for verifying the ligand-binding residues.

Result

More than half of the structures studied showed involvement of prosequences with the cognate protein in terms of residue interactions. Fourteen of these structures werepredicted to have various binding site pockets. Out of these, seven structures were found to have prosequence residues involved in ligand binding.

Conclusion

Our studies show that, along with interacting with the cognate protein, N-terminal prosequences also participate in the formation of the binding pockets and interactions with ligands. Binding pockets formed in the protein part are also influenced by the prosequence, indicating their possible structural role imparting functional assistance.