Author(s): Ferreira, Sofia ; Guedes, Joana P. ; Rocha, Juliana F. ; Sousa, Sérgio F. ; Rodrigues, L. R. ; Côrte-Real, Manuela ; Soares, Pedro ; Cátia S. Pereira
Date: 2025
Persistent ID: https://hdl.handle.net/1822/95207
Origin: RepositóriUM - Universidade do Minho
Lactoferrin (LF) is a multifunctional protein involved in critical biological processes such as immune response, antimicrobial activity, and iron regulation [1]. Its diverse roles include inhibiting inflammation, infections, and carcinogenesis [2], as well as modulating cellular processes by targeting proton-pumping ATPases such as V-ATPases in cancer cells [3], F- ATPases in bacteria [4], and P-ATPases in yeast [5]. Despite its inclusion in commercial products like toothpastes, infant formulas, and cosmetics, and its broad therapeutic potential [1;6], the mechanisms underlying LF's interactions with binding partners remain underexplored. Moreover, its evolutionary trajectory across species is poorly understood, leaving significant gaps in our knowledge of its biological diversity and potential applications. This study aims to bridge these gaps by conducting a comprehensive review of LF binding partners and their functional annotations, alongside an evolutionary analysis of LF among diverse species. By integrating bioinformatics and computational tools, we seek to elucidate LF's interactions with binding partners, uncover evolutionary relationships with homologous proteins and identify conserved motifs critical for LF-ATPase interactions. Our methodology includes the compilation and annotation of LF binding partners, functional characterization and interaction network analysis, and phylogenetic reconstruction of LF homologs using advanced computational approaches. This integrative approach leverages databases like STRING, EggNOG, and KEGG, alongside phylogenetic tools such as MEGA and BEAST. Overall, this study provides a comprehensive view of LFs functional landscape, highlighting its role as a critical regulator of essential biological processes. Preliminary data in LF evolutionary history also contributes to enhance our understanding of LF's multifaceted biological roles.
