Functional mapping of apidaecin through secondary structure correlation.

The mechanism through which apidaecin (GNNRPVYIPQPRPPHPRL) like proline rich, non-helical, antibacterial peptides penetrate into the bacterial cells is not yet clearly understood. To comprehend their transport across the bacterial cells, a detailed structure-activity correlation of apidaecin and its selected analogs is undertaken. In membrane like environment apidaecin exhibits a structural change which is mislaid in its biologically inactive P11-->Q substitution analog. This new structure, acquired by apidaecin but not by P11-->Q might be responsible for the difference in their antibacterial response. With this suggestion we explored the membrane permeation response of both by incubating them with small unilamellar vesicles (SUV). Unlike apidaecin, the P11-->Q did not induce leakage from SUV. To confirm whether this response is due to the substitution of P11-->Q of PQP motif, we chose P-ab (YVPLPNVPQPGRRPFPT), an N-terminal domain of abaecin which is homologous to apidaecin in terms of all prolines including conserved PQP, for comparison. Unlike P11-->Q but like apidaecin, P-ab also permeablized the SUV. Computational analysis also indicated that this particular mutation has a strong structural impact. These results led us to hypothesize that in bacterial environment apidaecin undergoes an ordered structural change that facilitates its entry into the bacterial membrane and also that PXP motives are important for this structural change. Apidaecin analogs not viable to organize/transform into this functionally active conformation are deleteriously affected. Adaptation to a unique conformation though insufficient (since functional binding with intracellular targets is also mandatory) seems to be an important prerequisite for the manifestation of full spectrum of antibacterial activity of apidaecin like peptides.