How proteins in a cell extract and use the energy from ATP
Adenosine triphosphate (ATP): Adenosine triphosphate (ATP) is considered by biologists to be the energy currency of life. It is the high-energy molecule that stores the energy we need. It is present in the cytoplasm and nucleoplasm of every cell, and essentially all the physiological mechanisms that require energy for operation obtain it directly from the stored ATP. It is a nucleotide. (Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA.) Each cell in the human body contains about a billion ATP molecules, and the power derived from the breakdown of them is used to deliver substances to their cellular homes, build needed complex molecules and even make muscles contract.
In the structure of ATP the part that is really critical is the phosphorous part – the triphosphate. The removal of one of these phosphate groups from the end, so that there are just two phosphate groups (i.e. converting ATP to ADP), liberates about 7.3 kilocalories per mole = 30.6 kJ/mol. This is about the same as the energy in a single peanut. Thus this conversion of ATP to ADP is an extremely crucial reaction for the supplying of energy for life processes. As food in the cells is gradually oxidized, the released energy is used to re-form the ATP from ADP so that the cell always maintains a supply of ATP.
Source: http://hyperphysics.phy-astr.gsu.edu/hbase/Biology/atp.html
Kinesins are a class of motor proteins that move along microtubule cables (cellular roadways) powered by the hydrolysis of ATP and convert chemical energy into mechanical work. The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cargo such as axonal transport.
How proteins in a cell extract and use the energy from ATP
Researchers from the Louisiana State University Health Sciences Center shed light on how proteins in a cell extract and use the energy from ATP.
The team chose to investigate kinesins that break down ATP. They narrowed their study to the human kinesin Eg5, which is essential for cell division. Associate professor Sunyoung Kim, who led the research work says, “We picked kinesins because they’re the simplest known motor proteins. Usually, proteins that break down ATP are very large and have a lot of moving parts for mechanical work. The simpler and the smaller the system is, the more likely you can capture information about it in detail.”
According to one of the researchers, assistant professor David Worthylake, to get a clear picture of how the kinesin and ATP interact, the team used X-ray crystallography to develop a three-dimensional structure that would detail all the bonds and atomic contacts.
Their strategy was to trap the protein in the middle of the energy-releasing chain of events by coaxing it to hold onto a chemical mimic of ATP, in which the final phosphate cannot be removed as usual, and examining the “jammed” protein up close. This according to another one of the researchers, Courtney Parke, a graduate student, was a challenge. She says successfully trapping an ATP mimic is quite difficult.
Further complicating matters, purified kinesin proteins typically are found bound to product of ATP breakdown, adenosine diphosphate, or ADP. So instead of inserting the mimic of ATP into this purified kinesin protein with ADP already bound to it, the researchers first pulled the ADP out and then asked the Eg5 kinesin to bind the ATP mimic.
The surprising result was that the protein uses a string of water molecules to harness the energy of the reaction.
Another researcher, assistant professor Edward Wojcik, notes “Conventional wisdom pointed toward the reactive agent that starts the ATP breakdown process as being something in the protein, such as an amino acid.” To the surprise of the researchers it wasn’t an amino acid at all: It was a second water molecule that pulled the proton off the first water molecule.
Kim explains, “Each of these water molecules is attached to different part of the protein. And, normally, they hold tightly to each other as well, keeping two very distant parts of the protein connected by a molecular bridge. Our data show, when the second water molecule takes the proton from the first one, the proton is transferred across this bridge. This causes the two different parts of the protein that the bridge holds together to unfurl, and you have motion in the protein.” That internal motion propels the nanomachine along its assigned roadway, allowing it to do its assigned duties. Wojcik says, “For such a relatively simple molecule, water still has some tricks to teach us, and I am still amazed that we found it to play such a pivotal role in the motor protein machinery.”
The team hopes that, with a clearer understanding of how these biological machines work, scientists will better understand how and why things are moved around inside cells, allowing them to figure out how to turn things on and off at will with novel drugs to help combat diseases.
“We believe many, if not all, proteins that use the energy from ATP breakdown may work the same way,” Kim says.
March 1, 2010