General Chemistry

Channels in Ferritin

Once the iron is soluble (as Fe(H2O)62+), how does it leave the ferritin shell? Recall that ferritin has two types of channels, three-fold and four-fold, in the shell. The soluble Fe2+ ion exits through the three-fold channels (Figure 12, below). These channels have a special property, known as polarity, that enables the passage of Fe2+ ions through these channels.

Polarity refers to significant differences in electronegativity between adjacent atoms in a molecule. For instance, the hydroxyl (-OH) functional group consists of an oxygen atom, which is highly electronegative, covalently bound to a hydrogen atom, which is much less electronegative. The highly electronegative oxygen atom draws the (negatively-charged) electrons in the bond to itself more than the less electronegative hydrogen atom does. Hence, the oxygen atom has a slight negative charge relative to the hydrogen atom. The bond between the oxygen and hydrogen atoms is then said to be polar, because it contains a negative pole (the oxygen) and a positive pole (the hydrogen). Because opposite charges attract one another, polar molecules interact well with other polar molecules and charged particles. The negative poles attract positive ions or the positive poles of other polar molecules, while the positive poles attract negative ions or the negative poles of other polar molecules.

Some amino acids have side chains that contain polar groups; these amino acids are known as polar amino acids. (Examination of the amino-acid structure in Figure 3 shows that all amino acids have an amino group and a carboxylic-acid group, which are polar. However, these polar groups form part of the backbone and do not contribute to the polarity of an amino-acid residue in a peptide. Only the side chain determines whether or not the amino acid is considered polar.) The three-fold channel in ferritin is lined with the polar amino acids aspartate (Asp) and glutamate (Glu) (Figure 13, below). Because it is lined with polar amino-acid side chains, the three-fold channel is also said to be polar. The channel's polarity allows it to interact favorably with the Fe2+ ion and with water, because the positive charge of the ion (or the positive pole of water) attracts the negative poles of the side chains (Figure 11). The favorable interaction allows Fe2+ to pass through the channel.

dipole moments

Figure 11

This diagram shows the interaction of a polar water molecule with the polar side chain of aspartate (an amino acid). This figure uses the standard depiction of the direction of polarity: an arrow pointing in the direction of the partial negative charge, with a + sign at the pole with a partial positive charge. In addition, the symbols "d-" and "d+" may be used to depict the negative and positive poles, respectively.

Fe(II) is probably not accompanied by all six water molecules of the hydrated complex as it passes through the channel, because this entire complex would be too large to fit through the channel. Most likely, Fe(II) is coordinated to some water molecules and to some of the polar side chains lining the channel as it passes from the inside to the outside of the ferritin shell. Once outside the shell, the Fe(II) then regains the six water molecules and is again solvated as Fe(H2O)62+.

3-fold channel glutamate polar amino acids glutamate

Figure 12

This is a molecular representation of the three-fold (polar) channel in the ferritin protein. Fe(II) can leave the ferritin shell through this channel.

Note: The amino acids that line the channel are shown in the CPK representation, and the remaining portions of the three peptide subunits that form the channel are shown in the ribbon representation.

Figure 13

This is a 2D-ChemDraw representation of aspartate (Asp) and glutamate (Glu), the polar amino acids that line the three-fold channels in ferritin. The side chains are shown in green. Recall that only the side-chain groups contribute to the polarity of the residue in a peptide.

Note: To view these amino acids interactively, please use Jmol, and click on the molecule above.

What about the other type of channels in ferritin, the four-fold channels (Figure 14) These channels are lined with the nonpolar amino acid leucine (Leu, Figure15). The side chain of leucine contains only carbon and hydrogen atoms, which have similar electronegativities. Hence, the four-fold channel is considered to be nonpolar. Because it is nonpolar, this channel does not interact favorably with the Fe2+ ion, and Fe2+ does not leave the ferritin shell through these channels. Rather, it is thought that these channels function as the site of electron transfer, whereby the Fe(III) in the mineral lattice is reduced to Fe(II). However, the mechanism of this electron transfer is not well understood.

4-fold channel
Leucine

Figure 14

This is a molecular representation of the four-fold (nonpolar) channel in the ferritin protein. Electrons are transferred via this channel to reduce the Fe(III) in the mineral lattice to Fe(II), thereby rendering the iron soluble so that it can be released from ferritin through the three-fold channel shown above (Figure 11).

Note: The amino acids that line the channel are shown in the CPK representation, and the remaining portions of the four peptide subunits that form the channel are shown in the ribbon representation.

Figure 15

This is a 2D-ChemDraw representation of leucine (Leu), the nonpolar amino acid that lines the four-fold channels in ferritin. The side chain is shown in green. Recall that only the side-chain groups contribute to the polarity of the residue in a peptide.

Note: To view this amino acid interactively, please use Jmol, and click on the molecule above.

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Revised: 2004-08-08