We modeled Cry1C toxin and its Aminopeptidase-N receptor and in silico docking analysis was performed. Further, we utilized biopanning against Cryl C followed by blocking assays and mutagenesis analysis to identify the binding epitope of SIAPN. We have identified a putative SIAPN binding region, APN-CRY (128HLHFHLP134). A derivative of SIAPN carrying the 1281-ILHFHLP134 region termed as binding region of APN (BR-APN) was cloned and its involvement in Cryl C binding and toxicity was checked. Cryl C-BRAPN binding was competed by synthetic peptides homologous to loop2 and loop3 of domain II but not by that of loopa. Additionally, alanines substitution of residues H128, H130, H132 and P134 affect the binding efficiency of receptor to Cryl C toxin (upto 4-fold lower affinity).These residues are also implicated in Cryl C toxicity as shown by the reduced ability to affect the mortality of Cryl C on S. litura larvae when toxin was preincubated with a fragment of the receptor. (C) 2014 Elsevier Ltd. All rights reserved.