Lactoferrin and transferrin: Functional variations on a common structural framework

Abstract

Lactoferrin shares many structural and functional features with serum transferrin, including an ability to bind iron very tightly, but reversibly, a highly-conserved three-dimensional structure, and essentially identical iron-binding sites. Nevertheless, lactoferrin has some unique properties that differentiate it: an ability to retain iron to much lower pH, a positively charged surface, and other surface features that give it additional functions. Here, we review the structural basis for these similarities and differences, including the importance of dynamics and conformational change, and specific interactions that regulate iron binding and release.

Dealing with iron: Common structural principles in proteins that transport iron and heme

“…Only sTf has a proven transport function, but all transferrins function to control the levels of free iron in the locations where they are found. Lf, for example, is present in milk, many other exocrine secretions, and white blood cells, and binds iron even more tightly than does sTf (6) and retains it to lower pH (7); its function appears to be primarily protective (8). The role of mTf, which is found in both membrane-bound and soluble forms (9), is uncertain but clearly relates in some way to the control of iron.…”

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

“…Lactoferrin (LF) is a multifunctional protein belonging to the transferrin family. The levels of transferrin have been shown to increase in iron deficiency anemia [5,6]. Additionally, incidents of bleeding in cancer patients can result in iron deficiency anemia, which subsequently increases the levels of lactoferrin [7–9].…”

Bovine lactoferrin region responsible for binding to bifidobacterial cell surface proteins

“…This 80 kDa protein is composed of a single polypeptide chain of about 690 amino acid residues and is folded into two homologous (~ 40% sequence identity) lobes, representing its N-and C-terminal halves and connected by a short "hinge" peptide of 10-15 residues. Each lobe has two domains (N1 and N2, C1 and C2) and can bind a single ferric ion concomitantly with one bicarbonate ion very tightly [2]. There are striking conservation between these two lobes in respect of their iron retention ability (C-lobe bind iron more tightly) [3] and biological functions (some functions of Lf are thought to be involved in the N-lobe) [4,5].…”