Platinum complexes such as the well-known cisplatin are powerful antitumor medications.
They cross the cell membrane and reach the nucleus, where they attach to DNA and stop cell growth. But how does cisplatin get to the nucleus? Italian researchers have now proven that a copper transport protein may play a critical role. In the journal Angewandte Chemie, they present their hypothesis about the transport mechanism.
It has always been assumed that cisplatin simply passes through the cell membrane; however, growing evidence indicates that a copper transporter is involved. Ctr1 is a membrane-dwelling protein that brings copper into cells. It consists of three helical segments that sit in the membrane, one end protruding into the cell, the other on the outside. Three such molecules lodge together to form a channel-like structure. The end that sticks out of the cell and the interior of the “channel” contain many sulfur-containing methionine groups, which are important for binding copper.
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.
Author: Giovanni Natile, Università degli Studi di Bari (Italy), mailto:firstname.lastname@example.org
Title: Interaction between Platinum Complexes and a Methionine Motif Found in Copper Transport Proteins
Angewandte Chemie International Edition, doi: 10.1002/anie.200703271
| Angewandte Chemie
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Physics and Astronomy
30.03.2017 | Studies and Analyses
30.03.2017 | Life Sciences