The Natterin Proteins Diversity: A Review on Phylogeny, Structure, and Immune Function

Author(s)

Lima, Carla ^[1] ; Disner, Geonildo Rodrigo ^[1] ; Falcao, Maria Alice Pimentel ^[1] ; Seni-Silva, Ana Carolina ^{[2, 1]} ; Maleski, Adolfo Luis Almeida ^{[2, 1]} ; Souza, Milena Marcolino ^[1] ; Reis Tonello, Mayara Cristina ^[1] ; Lopes-Ferreira, Monica ^[1]

Affiliation

^[1] Butantan Inst, Immunoregulat Unit, Lab Appl Toxinol CeTICs FAPESP, Vital Brasil Ave, 1500 Butantan, BR-05503900 Sao Paulo - Brazil

^[2] Butantan Inst, Postgrad Program Toxinol, BR-05503900 Sao Paulo - Brazil

• Document type: Review article
• Source: TOXINS; v. 13, n. 8 AUG 2021.
• Web of Science Citations: 0

Abstract

Since the first record of the five founder members of the group of Natterin proteins in the venom of the medically significant fish Thalassophryne nattereri, new sequences have been identified in other species. In this work, we performed a detailed screening using available genome databases across a wide range of species to identify sequence members of the Natterin group, sequence similarities, conserved domains, and evolutionary relationships. The high-throughput tools have enabled us to dramatically expand the number of members within this group of proteins, which has a remote origin (around 400 million years ago) and is spread across Eukarya organisms, even in plants and primitive Agnathans jawless fish. Overall, the survey resulted in 331 species presenting Natterin-like proteins, mainly fish, and 859 putative genes. Besides fish, the groups with more species included in our analysis were insects and birds. The number and variety of annotations increased the knowledge of the obtained sequences in detail, such as the conserved motif AGIP in the pore-forming loop involved in the transmembrane barrel insertion, allowing us to classify them as important constituents of the innate immune defense system as effector molecules activating immune cells by interacting with conserved intracellular signaling mechanisms in the hosts. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/27677-7 - Study of the induction of regulatory microRNAs by TNP dependent on Aryl hydrocarbon Receptor (AhR) activation
• Grantee: Geonildo Rodrigo Disner
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/02333-3 - Validation of the functional importance of natterins in the innate immune response in zebrafish by CRISPR-Cas9, a loss-of-function method
• Grantee: Ana Carolina de Seni Silva
• Support Opportunities: Scholarships in Brazil - Master