title: The sequence, structural, and functional diversity within a protein family and implications for specificity and safety: The case for ETX_MTX2 insecticidal proteins.
abstract: The need for sustainable insect pest control is driving the investigation and discovery of insecticidal proteins outside of the typical 3-domain Cry protein family from Bacillus thuringiensis (Bt). Examples include Cry35 and Cry51 that belong to protein families (Toxin_10, ETX_MTX2) sharing a common β-pore forming structure and function with known mammalian toxins such as epsilon toxin (ETX). Although β-pore forming proteins are related to mammalian toxins, there are key differences in sequence and structure that lead to organism specificity that is useful in the weight-of-evidence approach for safety assessment. Despite low overall amino acid sequence identity among ETX_MTX2 proteins, sequence and structural similarities are found in the tail region responsible for the shared oligomerization and pore formation functions (causing the "relatedness"). Conversely, most of the sequence and structural diversity is located in the head region that is likely responsible for differential receptor binding and target species specificity (e.g., insecticidal vs. mammalian). Therefore, inclusion of a domain-based protein characterization approach that includes bioinformatic and functional comparisons of conserved and diverse domains will enhance the overall weight of evidence safety assessment of proteins including recently reported Cry51 protein variants (Cry51Aa1, Cry51Aa2, and Cry51Aa2.834_16).
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States. Electronic address: william.moar@monsanto.com.
authors.forename: William J
authors.initials: WJ
authors.lastname: Moar
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Evans
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Colton R
authors.initials: CR
authors.lastname: Kessenich
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Baum
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bowen
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Edrington
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Haas
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Jean-Louis K
authors.initials: JK
authors.lastname: Kouadio
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: James K
authors.initials: JK
authors.lastname: Roberts
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Andre
authors.initials: A
authors.lastname: Silvanovich
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Weiner
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Glenn
authors.affiliation: Monsanto Co., 800 North Lindbergh Blvd., St. Louis, MO, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Odegaard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D004731:Endotoxins / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D007306:Insecticides / Q000737:chemistry / Q000145:classification* / Q000378:metabolism; D008958:Models, Molecular; D010572:Pest Control, Biological / Q000379:methods*; D013329:Structure-Activity Relationship
chemical_list: D004731:Endotoxins; D007306:Insecticides
keywords: Bacillus thuringiensis; Beta pore forming toxins; Bioinformatics; Cry51; ETX/MTX2 Pfam; Lygus