The inositol 1,4,5-triphosphate receptor (IP3R), an IP3-gated Ca2+ release channel on the endoplasmic reticulum (ER) membrane, plays a critical role in maintaining cytosolic Ca2+ homeostasis in cells. Particularly, ATP increases IP3R activity by binding to ATPA, a putative glycine-rich Walker A-type motif (GXGXXG) specific to type 1 IP3R (IP(3)R1). Here, we established an efficient process to produce the ATPA containing domain of 1P(3)R1 (IP(3)R1-ATPA) using a chaperone co-expression system in Escherichia coil. The recombinant protein was well expressed as a soluble form and showed a high thermostability. Circular dichroism results indicated a mainly alpha-helical conformation of the purified protein. Additionally, model structures of IP(3)R1-ATPA were calculated and validated using different modeling algorithms. The structural models of IP(3)R1-ATPA not only supported the observed high thermostability, but also suggested a potential ATP binding site. (C) 2015 Elsevier Ltd. All rights reserved.