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
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research