The Amino Acids that bind and hold iron in a N-terminus Transferrin
Transferrin's primary protein structure is made up of about
700 amino acids (80 kDa). Transferrin has a combination of alpha
helices and beta sheets to form 2 different lobes: N- and C-
terminus. These two domains are held together by a short peptide
and create a deep hyrophobic site. The amino acids that bind the
Ferric iron ion are the same for both lobes: two tyrosine residues, one
aspartic acid, and one histotine. The binding of iron also needs
an anion which is usually carbonate (CO32-).
The 3- charge, contributed by the two tyrosine and one aspartic acid,
balances the 3+ charge of Ferric iron. The charge on the anion is
balanced by the adjacent positive charge on the protein (in
transferrins, this postive charge comes from the arginine side chain
and the N-termins of an alpha helix).
The transferrin receptor is a
transmembrane homodimer consisting of 2 identical monomers. These
monomers are able to bind up to two molecules of transferrin. The
monomers are joined by 2 disulfind bonds at Cys89 and Cys89. This
structure contains a short NH2 terminal cytoplasmic region
(residues 1 to 67), a single transmembrane pass (residues 68 to
88), and a large extracellular ectodomain (residues 89 to 760).
The extracellular portion bears a trypsin-sensitive region and contains
a binding site for transferrin. The transferrin receptor is
butterfly-like in shape with three distinct domains: apical,
protease-like, and helical. The membrane stalk probably involves
disulfide bonded residues.
Transferrin and Transferrin Receptor
The binding affinity of diferric Tf for TfR is very high.
Research concludes that how and where Tf bind to TfR is not fully
understood. It was that the primary receptor is mainly in the
C-lobe of Rf. However, in recent studies, both the N- and
C- lobes are shown to play a role in Tf binding. In the TfR, the
helical domain is thought to be the major player in Tf binding. BackNext