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Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Human Insulin-like Peptide 5 (INSL5). Identification of a Simplified Version of Two-Chain Analog A13
Xiaozhou Zhang1, Ross A D Bathgate1, Mohammed Akhter Hossain1
1Florey Institute of Neuroscience and Mental Health, School of Biomedical Science, Department of Biochemistry and Molecular Biology and School of Chemistry, The University of Melbourne, Parkville, VIC 3052, Australia.
Abstract:
The receptor for insulin-like peptide 5 (INSL5), RXFP4, is a potential pharma target for treating human conditions such as constipation, anorexia, and obesity. However, since INSL5 has a complex structure of two chains and three disulfide bonds, its synthesis has proven to be extremely difficult via either chemical or recombinant approaches. Previous studies led to the engineering of a high yielding simplified INSL5 analog, named analog 13 (A13), which retains native INSL5-like activity. The focus of this study is to further simplify the structure of A13 by truncating the N-terminal residues of the B-chain. We have found that the first six residues at the N-terminus of A13 are not important for RXFP4 binding and cAMP potency. The most minimized active structure of INSL5 identified in this study is A13: B7-24 which will be an important research tool to study the physiological role of RXFP4 and a template for further modification to improve its pharmacokinetic properties.
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