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A team led by Giovanni Natile at the University of Bari (Italy) has
now proven that this structural element also plays a role in binding
platinum. The researchers produced a synthetic peptide with a
structure very similar to the extracellular end of the copper
transport protein. Cisplatin is a complex with a central platinum ion
and four ligands: two neighboring amino groups and two neighboring
chloride ions. The peptide displaces all four of these ligands and
binds to the platinum ion itself.
As is the case for copper, the transport protein seems to bind the
platinum atom from cisplatin by replacing all other ligands bound to
the metal ion. The next step could be the traversal of a ligand-free
�naked� platinum atom through the channel and into the cytosol of the
cell. However, this contradicts other experiments that have
demonstrated that treated tumor cells do not contain bare platinum,
but rather undegraded cisplatin - accumulated
in certain organelles.
Natile and his co-workers have proposed an interesting hypothesis to
explain these observations: After an initial interaction between a few
cisplatin molecules and the methionine-rich extracellular end of the
copper transporter, the platinum ion does not pass through the channel,
but instead stabilizes the trimeric channel structure. This sets in
motion a mechanism called endocytosis, in which the cell membrane
encircles the transporter and forms a little interior bubble filled
with the outer medium. This medium contains some intact cisplatin. The
bubble then migrates to the interior of the cell and comes into
contact with the organelles, including the nucleus.
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