Heme-binding of bovine lactoferrin: the potential presence of a heme-binding capacity in an ancestral transferrin gene

Abstract

Lactoferrin (Lf) and transferrin (Tf) are iron-binding proteins that can bind various metal ions. This study demonstrates the heme-binding activity of bovine Lf and Tf using biotinylated hemin. When both proteins were coated on separate plate wells, each directly bound biotinylated hemin. On the other hand, when biotinylated hemin was immobilized on an avidin-coated plate, soluble native Lf bound to the immobilized biotinylated hemin whereas native Tf did not, suggesting that a conformational change triggered by coating on the plate allows the binding of denatured Tf with hemin. Incubation of Lf with hemin-agarose resulted in negligible binding of Lf with biotinylated hemin. Lf in bovine milk also bound to immobilized biotinylated hemin. These results demonstrate that bovine Lf has specific heme-binding activity, which is different from Tf, suggesting that either Tf lost heme-binding activity during its evolution or that Lf evolved heme-binding activity from its Tf ancestral gene. Additionally, Lf in bovine milk may bind heme directly, but may also bind heme indirectly by interaction with other milk iron- and/or heme-binding proteins.

Bovine lactoferrin inhibits Plasmodium berghei growth by binding to heme

“…Lactoferrin is known to bind to various metal ions, notably iron 25 , including via potentially traditional and novel iron-binding sites 25 . Lactoferrin's potential to bind heme has also been elucidated by assessing its interaction with various milk proteins 26,27 . In hemozoin inhibition assays, the pH tends to be acidic.…”

“…Each examined transferrin type inhibited hemozoin formation. While both bLF and TF bind to heme, this potentially involves different mechanisms 26,27 , which may influence their respective capabilities.…”

Genome-wide association study and predictive ability for growth traits in Nellore cattle

“…The SLCO2A1 gene function was related to muscle growth metabolism in broilers (COUDERT et al, 2018). The SRPRB gene was associated with transferrin, an iron signal recognition (SR) subunit receptor particle in organs, which is encoded by the TF gene, being fundamental in muscle metabolism acting over growth, and cellular differentiation (ORINO, 2016;SAITO et al, 2018).…”